Pub Date : 2024-11-04DOI: 10.1016/j.bone.2024.117315
Tissue engineering employs the use of bioactive materials to facilitate the filling and acceleration of bone defect healing, thereby introducing novel concepts to the field of in situ bone repair. Some studies have shown that periosteum plays an important role in bone regeneration and repair. In this study, biomimetic periosteum-bone scaffolds were prepared by depositing poly-L-lactic acid (PLLA) electrospun fibers on the surface of the gelatin/chitosan cryogel to mimic the bone and periosteum structure, respectively. To improve the bioactivity of the scaffold, bone morphogenetic protein-2 (BMP-2) was loaded into a loose porous mesh-like cryogel, while platelet-derived growth factor-BB (PDGF-BB) was encapsulated in the core of PLLA nanofibers with core-shell structure. Both of these two growth factors were released locally at the site of bone defect, where they exert a synergistic effect on osteogenesis, thereby greatly accelerating bone healing. The in vitro experiments demonstrated that the biomimetic periosteum-bone scaffolds exhibited favourable biocompatibility and osteogenesis ability. Furthermore, the in vivo experiments indicated that the composite scaffold repaired rat skull defects in a more rapid and effective manner. In conclusion, biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB shows significant potential for bone regeneration.
{"title":"Biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB for skull repair","authors":"","doi":"10.1016/j.bone.2024.117315","DOIUrl":"10.1016/j.bone.2024.117315","url":null,"abstract":"<div><div>Tissue engineering employs the use of bioactive materials to facilitate the filling and acceleration of bone defect healing, thereby introducing novel concepts to the field of <em>in situ</em> bone repair. Some studies have shown that periosteum plays an important role in bone regeneration and repair. In this study, biomimetic periosteum-bone scaffolds were prepared by depositing poly-L-lactic acid (PLLA) electrospun fibers on the surface of the gelatin/chitosan cryogel to mimic the bone and periosteum structure, respectively. To improve the bioactivity of the scaffold, bone morphogenetic protein-2 (BMP-2) was loaded into a loose porous mesh-like cryogel, while platelet-derived growth factor-BB (PDGF-BB) was encapsulated in the core of PLLA nanofibers with core-shell structure. Both of these two growth factors were released locally at the site of bone defect, where they exert a synergistic effect on osteogenesis, thereby greatly accelerating bone healing. The <em>in vitro</em> experiments demonstrated that the biomimetic periosteum-bone scaffolds exhibited favourable biocompatibility and osteogenesis ability. Furthermore, the <em>in vivo</em> experiments indicated that the composite scaffold repaired rat skull defects in a more rapid and effective manner. In conclusion, biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB shows significant potential for bone regeneration.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.bone.2024.117314
Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.
{"title":"Exercise-induced interactions between skeletal muscle and bone via myokines and osteokine in mice: Role of FNDC5/irisin, IGF-1, and osteocalcin","authors":"","doi":"10.1016/j.bone.2024.117314","DOIUrl":"10.1016/j.bone.2024.117314","url":null,"abstract":"<div><div>Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.bone.2024.117307
The study aimed to evaluate the role of trabecular bone score (TBS) as determinant in the risk for vertebral fracture (VF) and define specific TBS threshold/s in women with postmenopausal osteoporosis.
We studied 107 women with postmenopausal osteoporosis characterized by L1-L4 T-score ≤ −3.0 with (group 1) and without (group 2) VF, or L1-L4 T-score ≤ −1.0 and ≥ −2.4 and multiple vertebral fractures (VF) (group 3). We assessed 30 postmenopausal women with L1-L4 T-score ≤ −1.0 and ≥ −2.4 and no VF as controls (group 4). We measured L1-L4, femoral neck and total hip areal bone mineral density (aBMD) by dual X-ray absorptiometry (DXA) (QDR 4500; Hologic, Waltham, MA) and calculated TBS from de-identified DXA L1-L4 scans by the TBS iNsight software (Medimaps, Geneva, Switzerland). The assessment of VF was performed by means of anteroposterior and left lateral standardized radiographs of the thoracic and lumbar spine. We calculated the FRAX® value in all subjects for the assessment of 10-year fracture risk for major and hip fractures.
Forty-two subjects with L1-L4 T-score ≤ −3.0 had at least one VF (group 1), while 41 have no VF (group 2). Twenty-four subjects had L1-L4 T-score ≤ −1.0 and ≥ −2.4 and at least 3 VF (group 3). We observed significantly lower TBS values in group 1 and group 3 compared to group 2 (p < 0.001) and group 4 (p < 0.05). L1-L4 aBMD and TBS values were not significantly associated in all groups. Interestingly, TBS values were independently associated with the presence of VF (log odds ratio − 8, p < 0.001) but not with the number of VF by the stepwise regression analysis. Furthermore, when we applied the cut-off value of TBS associated with degraded microarchitecture and elevated fracture risk (< 1.23), only 52 % of the subjects had VF. The cut-off value of TBS below which VF could be predicted was calculated by the receiver operating characteristic curve analysis and was 1.13.
Our study demonstrates an independent association between altered trabecular microarchitecture, assessed by TBS, and the occurrence of VF in postmenopausal women with osteoporosis. This association is significant for values of TBS lower than those reported by population-based studies. Cut-off values of TBS need further evaluation by specifically designed studies assessing disease- specific thresholds for fracture risk.
{"title":"Assessment of trabecular bone score (TBS) in the prediction of vertebral fracture in postmenopausal osteoporosis","authors":"","doi":"10.1016/j.bone.2024.117307","DOIUrl":"10.1016/j.bone.2024.117307","url":null,"abstract":"<div><div>The study aimed to evaluate the role of trabecular bone score (TBS) as determinant in the risk for vertebral fracture (VF) and define specific TBS threshold/s in women with postmenopausal osteoporosis.</div><div>We studied 107 women with postmenopausal osteoporosis characterized by L1-L4 T-score ≤ −3.0 with (group 1) and without (group 2) VF, or L1-L4 T-score ≤ −1.0 and ≥ −2.4 and multiple vertebral fractures (VF) (group 3). We assessed 30 postmenopausal women with L1-L4 T-score ≤ −1.0 and ≥ −2.4 and no VF as controls (group 4). We measured L1-L4, femoral neck and total hip areal bone mineral density (aBMD) by dual X-ray absorptiometry (DXA) (QDR 4500; Hologic, Waltham, MA) and calculated TBS from de-identified DXA L1-L4 scans by the TBS iNsight software (Medimaps, Geneva, Switzerland). The assessment of VF was performed by means of anteroposterior and left lateral standardized radiographs of the thoracic and lumbar spine. We calculated the FRAX® value in all subjects for the assessment of 10-year fracture risk for major and hip fractures.</div><div>Forty-two subjects with L1-L4 T-score ≤ −3.0 had at least one VF (group 1), while 41 have no VF (group 2). Twenty-four subjects had L1-L4 T-score ≤ −1.0 and ≥ −2.4 and at least 3 VF (group 3). We observed significantly lower TBS values in group 1 and group 3 compared to group 2 (<em>p</em> < 0.001) and group 4 (<em>p</em> < 0.05). L1-L4 aBMD and TBS values were not significantly associated in all groups. Interestingly, TBS values were independently associated with the presence of VF (log odds ratio − 8, p < 0.001) but not with the number of VF by the stepwise regression analysis. Furthermore, when we applied the cut-off value of TBS associated with degraded microarchitecture and elevated fracture risk (< 1.23), only 52 % of the subjects had VF. The cut-off value of TBS below which VF could be predicted was calculated by the receiver operating characteristic curve analysis and was 1.13.</div><div>Our study demonstrates an independent association between altered trabecular microarchitecture, assessed by TBS, and the occurrence of VF in postmenopausal women with osteoporosis. This association is significant for values of TBS lower than those reported by population-based studies. Cut-off values of TBS need further evaluation by specifically designed studies assessing disease- specific thresholds for fracture risk.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.bone.2024.117311
{"title":"Letter to the editor: “Exposure to low humidex increases the risk of hip fracture admissions in a subtropical coastal Chinese city”","authors":"","doi":"10.1016/j.bone.2024.117311","DOIUrl":"10.1016/j.bone.2024.117311","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.bone.2024.117310
Neutrophils have been extensively studied for their critical roles in supporting immune defense mechanisms, initiating bone regeneration, and promoting angiogenesis. Nonetheless, the influence of neutrophils on physiological conditions, particularly in the context of bone development, remains incompletely understood. In this study, we examined the effects of non-inflammatory neutrophils on bone physiology by depleting Ly6G+ neutrophils and inducing neutropenia through myelosuppression. Our results demonstrated a notable increase in bone mass and a decrease in the bone marrow cavity upon depletion of the neutrophils. These effects were attributed to the direct interaction between neutrophils and osteoblasts, independent of reduced secretion of typical inflammatory cytokines or diminished osteoclast differentiation. This observation suggests a non-inflammatory function of neutrophils within the endosteal microenvironment, where they regulate osteogenic differentiation to preserve optimal bone mass, shape healthy three-dimensional bone trabecular structures, and create ample space for hematopoietic niche development.
{"title":"Neutrophils inhibit bone formation by directly contacting osteoblasts and suppressing osteogenic differentiation","authors":"","doi":"10.1016/j.bone.2024.117310","DOIUrl":"10.1016/j.bone.2024.117310","url":null,"abstract":"<div><div>Neutrophils have been extensively studied for their critical roles in supporting immune defense mechanisms, initiating bone regeneration, and promoting angiogenesis. Nonetheless, the influence of neutrophils on physiological conditions, particularly in the context of bone development, remains incompletely understood. In this study, we examined the effects of non-inflammatory neutrophils on bone physiology by depleting Ly6G<sup>+</sup> neutrophils and inducing neutropenia through myelosuppression. Our results demonstrated a notable increase in bone mass and a decrease in the bone marrow cavity upon depletion of the neutrophils. These effects were attributed to the direct interaction between neutrophils and osteoblasts, independent of reduced secretion of typical inflammatory cytokines or diminished osteoclast differentiation. This observation suggests a non-inflammatory function of neutrophils within the endosteal microenvironment, where they regulate osteogenic differentiation to preserve optimal bone mass, shape healthy three-dimensional bone trabecular structures, and create ample space for hematopoietic niche development.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.bone.2024.117309
Despite its invasive character, bone biopsy followed by histomorphometry remains the gold standard for diagnosing and classifying many metabolic bone diseases. However, the interpretation of histomorphometric parameters requires comparison with average values obtained from a proper control group, which are only available for some populations, and reference standards still need to be published. Therefore, our objective was to estimate average values for bone histomorphometric parameters overall, by age, gender, and race (White and Black) categories of healthy adult individuals, based on a systematic review and meta-analysis of clinical studies. Relevant studies published in English with available results until December 2020 were identified by PubMed (Medline) search and consulting experts in the field. Out of 447 potentially relevant studies, 37 met the inclusion criteria. Meta-analysis using fixed-effects models was used to pool mean estimates and 95% confidence intervals (CI) for 16 bone histomorphometry parameters.
An age-by-gender trend was observed in most histomorphometry parameters. The mean estimates of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) decreased. In contrast, trabecular separation (Tb.Sp) increased from the youngest to the oldest age categories in both genders. Osteoblast surface (Ob.S/BS) and osteoclast surface (Oc.S/BS) decreased across all age categories in males. Mineralizing surface (MS/BS) increased from the youngest to the oldest age categories in females, while mineralization lag time (Mlt) increased in both genders. Furthermore, gender and race had a significant effect on several histomorphometry parameters.
In conclusion, this meta-analysis provided mean estimates for normal values of histomorphometric parameters that clinicians may use when evaluating bone biopsies in patients. This enables the direct comparison of patients' histomorphometric values with the suitable reference group regarding age, gender, and race.
{"title":"Histomorphometric parameters of iliac bone in healthy individuals: Systematic review and meta-analysis","authors":"","doi":"10.1016/j.bone.2024.117309","DOIUrl":"10.1016/j.bone.2024.117309","url":null,"abstract":"<div><div>Despite its invasive character, bone biopsy followed by histomorphometry remains the gold standard for diagnosing and classifying many metabolic bone diseases. However, the interpretation of histomorphometric parameters requires comparison with average values obtained from a proper control group, which are only available for some populations, and reference standards still need to be published. Therefore, our objective was to estimate average values for bone histomorphometric parameters overall, by age, gender, and race (White and Black) categories of healthy adult individuals, based on a systematic review and meta-analysis of clinical studies. Relevant studies published in English with available results until December 2020 were identified by PubMed (Medline) search and consulting experts in the field. Out of 447 potentially relevant studies, 37 met the inclusion criteria. Meta-analysis using fixed-effects models was used to pool mean estimates and 95% confidence intervals (CI) for 16 bone histomorphometry parameters.</div><div>An age-by-gender trend was observed in most histomorphometry parameters. The mean estimates of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) decreased. In contrast, trabecular separation (Tb.Sp) increased from the youngest to the oldest age categories in both genders. Osteoblast surface (Ob.S/BS) and osteoclast surface (Oc.S/BS) decreased across all age categories in males. Mineralizing surface (MS/BS) increased from the youngest to the oldest age categories in females, while mineralization lag time (Mlt) increased in both genders. Furthermore, gender and race had a significant effect on several histomorphometry parameters.</div><div>In conclusion, this meta-analysis provided mean estimates for normal values of histomorphometric parameters that clinicians may use when evaluating bone biopsies in patients. This enables the direct comparison of patients' histomorphometric values with the suitable reference group regarding age, gender, and race.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.bone.2024.117306
<div><h3>Background</h3><div>The risk of fractures is increased in persons with type 1 diabetes (T1D) and assessment of bone health has been included in the 2024 updated Standards of Care by The American Diabetes Association (ADA). Previous studies have found that in T1D bone metabolism, mineral content, microstructure, and strength diverge from that of persons without diabetes. However, a clear description of a T1D bone phenotype has not yet been established. We investigated bone mechanical properties and microstructure in T1D compared with healthy controls. For the potential future introduction of additional bone measures in the clinical fracture risk assessment, we aimed to assess any potential associations between various measures related to bone indices in subjects with T1D.</div></div><div><h3>Methods</h3><div>We studied human bone indices in a clinical cross-sectional setup including 111 persons with early-onset T1D and 37 sex- and age-matched control persons. Participants underwent hip and spine DXA scans for bone mineral density (BMD) of the femoral neck (FN), total hip (TH), and lumbar spine (LS), and TBS evaluation, microindentation of the tibial shaft for Bone Material Strength index (BMSi), and high-resolution periphery quantitative computed tomography (HRpQCT) of the distal radius and tibia for volumetric BMD (vBMD) and structural measures of trabecular and cortical bone. Results are reported as means with (standard deviation) or (95% confidence intervals (CI)), medians with [interquartile range], and differences are reported with (95% CI).</div></div><div><h3>Results</h3><div>The study included 148 persons aged 20 to 75 years with a median age of 43.2 years. The T1D group who had all been diagnosed with T1D before the age of 18 years demonstrated values of HbA1c ranging from 39 to 107 mmol/mol and a median HbA1c of 57 mmol/mol. The BMD did not differ between groups (the mean difference in FN-BMD was 0.026 g/cm<sup>2</sup> (−0.026; 0.079), <em>p</em> = 0.319) and the median BMSi was comparable in the two groups (79.2 [73.6; 83.8] in the T1D group compared with 77.9 [70.5, 86.1] in the control group). Total and trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), and trabecular thickness (Tb.Th) of both radius and tibia were lower in participants with T1D. The mean Tb.vBMD at the radius was 143.6 (38.5) mg/cm<sup>3</sup> in the T1D group and 171.5 (37.7) mg/cm<sup>3</sup> in the control group, <em>p</em> < 0.001. The mean Ct. Th<sup>d</sup> of the radius was 0.739 mm (0.172) in the T1D group and 0.813 (0.188) in the control group, <em>p</em> = 0.044. Crude linear regressions revealed limited agreement between BMSi and Tb.vBMD (<em>p</em> = 0.010, r<sup>2</sup> = 0.040 at the radius and <em>p</em> = 0.008, r<sup>2</sup> = 0.040 at the tibia and between BMSi and the estimated failure load (FL) at the tibia (<em>p</em> < 0.001, r<sup>2</sup> = 0.090). There were no significant correlations between BMSi and Ct.Th. TBS correlated
{"title":"Bone properties in persons with type 1 diabetes and healthy controls – A cross-sectional study","authors":"","doi":"10.1016/j.bone.2024.117306","DOIUrl":"10.1016/j.bone.2024.117306","url":null,"abstract":"<div><h3>Background</h3><div>The risk of fractures is increased in persons with type 1 diabetes (T1D) and assessment of bone health has been included in the 2024 updated Standards of Care by The American Diabetes Association (ADA). Previous studies have found that in T1D bone metabolism, mineral content, microstructure, and strength diverge from that of persons without diabetes. However, a clear description of a T1D bone phenotype has not yet been established. We investigated bone mechanical properties and microstructure in T1D compared with healthy controls. For the potential future introduction of additional bone measures in the clinical fracture risk assessment, we aimed to assess any potential associations between various measures related to bone indices in subjects with T1D.</div></div><div><h3>Methods</h3><div>We studied human bone indices in a clinical cross-sectional setup including 111 persons with early-onset T1D and 37 sex- and age-matched control persons. Participants underwent hip and spine DXA scans for bone mineral density (BMD) of the femoral neck (FN), total hip (TH), and lumbar spine (LS), and TBS evaluation, microindentation of the tibial shaft for Bone Material Strength index (BMSi), and high-resolution periphery quantitative computed tomography (HRpQCT) of the distal radius and tibia for volumetric BMD (vBMD) and structural measures of trabecular and cortical bone. Results are reported as means with (standard deviation) or (95% confidence intervals (CI)), medians with [interquartile range], and differences are reported with (95% CI).</div></div><div><h3>Results</h3><div>The study included 148 persons aged 20 to 75 years with a median age of 43.2 years. The T1D group who had all been diagnosed with T1D before the age of 18 years demonstrated values of HbA1c ranging from 39 to 107 mmol/mol and a median HbA1c of 57 mmol/mol. The BMD did not differ between groups (the mean difference in FN-BMD was 0.026 g/cm<sup>2</sup> (−0.026; 0.079), <em>p</em> = 0.319) and the median BMSi was comparable in the two groups (79.2 [73.6; 83.8] in the T1D group compared with 77.9 [70.5, 86.1] in the control group). Total and trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), and trabecular thickness (Tb.Th) of both radius and tibia were lower in participants with T1D. The mean Tb.vBMD at the radius was 143.6 (38.5) mg/cm<sup>3</sup> in the T1D group and 171.5 (37.7) mg/cm<sup>3</sup> in the control group, <em>p</em> < 0.001. The mean Ct. Th<sup>d</sup> of the radius was 0.739 mm (0.172) in the T1D group and 0.813 (0.188) in the control group, <em>p</em> = 0.044. Crude linear regressions revealed limited agreement between BMSi and Tb.vBMD (<em>p</em> = 0.010, r<sup>2</sup> = 0.040 at the radius and <em>p</em> = 0.008, r<sup>2</sup> = 0.040 at the tibia and between BMSi and the estimated failure load (FL) at the tibia (<em>p</em> < 0.001, r<sup>2</sup> = 0.090). There were no significant correlations between BMSi and Ct.Th. TBS correlated ","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.bone.2024.117303
Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although in vitro studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass in vivo remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype via an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling. BMP3b null mice were viable, and exhibited no significant difference in body size compared to wildtype control. Trabecular bone parameters assessed by histomorphometry and μCT, revealed a significant increase in bone volume and bone mineral density. Expression of osteoblast-differentiation genes were elevated in bone tissue of BMP3b null mice, whereas expression of osteoclast-related genes remained unchanged. Consistent with this, Bmp3b was highly expressed in osteoblasts relative to osteoclast cells. Ex-vivo culture of primary bone marrow mesenchymal stem cells (BMSCs) and primary bone marrow-derived osteoclasts revealed that inactivation of BMP3b enhances osteogenesis without affecting osteoclastogenesis. Mechanistically, we found that BMP3b suppressed BMP4-induced Smad1/5 phosphorylation and inhibited the activity of a BMP4-driven Id-1 luciferase reporter. Protein-protein interaction assays revealed that BMP3b competitively interfered with the association of BMP4 and BMP type I receptors. These findings suggest that BMP3b regulates bone mass by acting as a BMP receptor antagonist. Thus, maintenance of bone mass involves antagonism of canonical BMP/Smad signaling by a member of the BMP family.
{"title":"BMP3b regulates bone mass by inhibiting BMP signaling","authors":"","doi":"10.1016/j.bone.2024.117303","DOIUrl":"10.1016/j.bone.2024.117303","url":null,"abstract":"<div><div>Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although <em>in vitro</em> studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass <em>in vivo</em> remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype <em>via</em> an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling. BMP3b null mice were viable, and exhibited no significant difference in body size compared to wildtype control. Trabecular bone parameters assessed by histomorphometry and μCT, revealed a significant increase in bone volume and bone mineral density. Expression of osteoblast-differentiation genes were elevated in bone tissue of BMP3b null mice, whereas expression of osteoclast-related genes remained unchanged. Consistent with this, <em>Bmp3b</em> was highly expressed in osteoblasts relative to osteoclast cells. <em>Ex-vivo</em> culture of primary bone marrow mesenchymal stem cells (BMSCs) and primary bone marrow-derived osteoclasts revealed that inactivation of BMP3b enhances osteogenesis without affecting osteoclastogenesis. Mechanistically, we found that BMP3b suppressed BMP4-induced Smad1/5 phosphorylation and inhibited the activity of a BMP4-driven Id-1 luciferase reporter. Protein-protein interaction assays revealed that BMP3b competitively interfered with the association of BMP4 and BMP type I receptors. These findings suggest that BMP3b regulates bone mass by acting as a BMP receptor antagonist. Thus, maintenance of bone mass involves antagonism of canonical BMP/Smad signaling by a member of the BMP family.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.bone.2024.117297
Craniofacial morphogenesis depends on complex cell fate decisions during the differentiation of post-migratory cranial neural crest cells. Molecular mechanisms of cell differentiation of mesenchymal cells to developing bones, cartilage, teeth, tongue, and other craniofacial tissues are still poorly understood. We performed single-cell transcriptomic analysis of craniofacial mesenchymal cells derived from cranial NCCs in mouse embryo. Using FACS sorting of Wnt1-Cre2 progeny, we carefully mapped the cell heterogeneity in the craniofacial region during the initial stages of cartilage and bone formation. Transcriptomic data and in vivo validations identified molecular determinants of major cell populations involved in the development of lower and upper jaw, teeth, tongue, dermis, or periocular mesenchyme. Single-cell transcriptomic analysis of Meis2-deficient mice revealed critical gene expression differences, including increased osteogenic and cell adhesion markers. This leads to affected mesenchymal cell differentiation and increased ossification, resulting in impaired bone, cartilage, and tongue formation.
{"title":"Single-cell transcriptomic resolution of osteogenesis during craniofacial morphogenesis","authors":"","doi":"10.1016/j.bone.2024.117297","DOIUrl":"10.1016/j.bone.2024.117297","url":null,"abstract":"<div><div>Craniofacial morphogenesis depends on complex cell fate decisions during the differentiation of post-migratory cranial neural crest cells. Molecular mechanisms of cell differentiation of mesenchymal cells to developing bones, cartilage, teeth, tongue, and other craniofacial tissues are still poorly understood. We performed single-cell transcriptomic analysis of craniofacial mesenchymal cells derived from cranial NCCs in mouse embryo. Using FACS sorting of Wnt1-Cre2 progeny, we carefully mapped the cell heterogeneity in the craniofacial region during the initial stages of cartilage and bone formation. Transcriptomic data and in vivo validations identified molecular determinants of major cell populations involved in the development of lower and upper jaw, teeth, tongue, dermis, or periocular mesenchyme. Single-cell transcriptomic analysis of <em>Meis2</em>-deficient mice revealed critical gene expression differences, including increased osteogenic and cell adhesion markers. This leads to affected mesenchymal cell differentiation and increased ossification, resulting in impaired bone, cartilage, and tongue formation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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