Bone最新文献

{"title":"Static histomorphometry parameters can identify bone turnover status in children and adults with chronic kidney disease","authors":"Jan M. Hughes-Austin ,&nbsp;Renata C. Pereira ,&nbsp;Vanda D. Jorgetti ,&nbsp;Isidro B. Salusky ,&nbsp;Joachim H. Ix","doi":"10.1016/j.bone.2024.117329","DOIUrl":"10.1016/j.bone.2024.117329","url":null,"abstract":"<div><h3>Introduction</h3><div>Tetracycline labeling for bone biopsy facilitates quantification of the pace of new bone production. As tetracycline labeling needs to be done prior to biopsy, it cannot be used to assess bone turnover in patients presenting with fractures, yet knowing turnover rate in patients experiencing fractures - especially in those with chronic kidney disease (CKD) - may guide appropriate medical therapy after surgical repair. Therefore, we sought to determine the diagnostic accuracy of static markers of bone turnover relative to tetracycline labeling in a pediatric and adult cohort of patients with chronic kidney disease (CKD) undergoing iliac crest biopsy with histomorphometry.</div></div><div><h3>Methods</h3><div>We evaluated two cohorts, one of 147 children and young adults ages 18±10 and another of 151 adults ages 49±13 who had undergone iliac crest biopsy with tetracycline labeling for clinical indications of CKD-mineral and bone disorders. We used bone formation rate relative to bone surface (BFR/BS) based on double tetracycline labeling as our gold standard marker of bone turnover. A blinded investigator used light microscopy without fluorescence to measure static bone turnover parameters. We compared the area under the ROC curve (AUC), sensitivity, and specificity of each static parameter with low and high bone turnover based on BFR/BS.</div></div><div><h3>Results</h3><div>In the pediatric and adult cohorts, 35 (24 %) and 70 (46 %) had low bone turnover, respectively, and 18 (12 %) and 30 (20 %) had high bone turnover, respectively. The static parameters with the greatest AUCs for low and high turnover were osteoblast surface/bone surface (Ob.S/BS), osteoclast surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV), and osteoid thickness (O.Th.) in both cohorts. Ob.S/BS had the highest AUC for low and high turnover in the pediatric cohort (0.8204 and 0.8678, respectively) whereas Oc.S/BS had the highest AUC for low turnover (0.8325) and ES/BS had the highest AUC for high turnover (0.7360) in the adult cohort.</div></div><div><h3>Discussion</h3><div>Static measures of histomorphometry that do not rely on tetracycline bone labeling can identify low and high bone turnover in children and adults with CKD with moderate to high accuracy. This approach may allow assessment of bone turnover in the setting of clinical fractures where clinicians may have access to bone tissue but where tetracycline labeling is not available.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117329"},"PeriodicalIF":3.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634327","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}

{"title":"Innate immune response to bone fracture healing","authors":"Jane Burgan ,&nbsp;Maryam Rahmati ,&nbsp;Mark Lee ,&nbsp;Augustine Mark Saiz","doi":"10.1016/j.bone.2024.117327","DOIUrl":"10.1016/j.bone.2024.117327","url":null,"abstract":"<div><div>The field of osteoimmunology has primarily focused on fracture healing in isolated musculoskeletal injuries. The innate immune system is the initial response to fracture, with inflammatory macrophages, cytokines, and neutrophils arriving first at the fracture hematoma, followed by an anti-inflammatory phase to begin the process of new bone formation. This review aims to first discuss the current literature and knowledge gaps on the immune responses governing single fracture healing by encompassing the individual role of macrophages, neutrophils, cytokines, mesenchymal stem cells, bone cells, and other immune cells. This paper discusses the interactive effects of these cellular responses underscoring the field of osteoimmunology. The critical role of the metabolic environment in guiding the immune system properties will be highlighted along with some effective therapeutics for fracture healing in the context of osteoimmunology. However, compared to isolated fractures, which frequently heal well, long bone fractures in over 30 % of polytrauma patients exhibit impaired healing. Clinical evidence suggests there may be distinct physiologic and inflammatory pathways altered in polytrauma resulting in nonunion. Nonunion is associated with worse patient outcomes and increased societal healthcare costs. The dysregulated immunomodulatory/inflammatory response seen in polytrauma may lead to this increased nonunion rate. This paper will investigate the differences in immune response between isolated and polytrauma fractures. Finally, future directions for fracture studies are explored with consideration of the emerging roles of newly discovered immune cell functions in fracture healing, the existing challenges and conflicting results in the field, the translational potential of these studies in clinic, and the more complex nature of polytrauma fractures that can alter cell functions in different tissues.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117327"},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634270","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}

{"title":"Multiple vertebral fractures after antiosteoporotic medications discontinuation: A comparative study to evaluate the potential rebound effect of denosumab","authors":"Mar Martín-Pérez ,&nbsp;Beatriz Sánchez-Delgado ,&nbsp;Patricia García-Poza ,&nbsp;Sergio López-Álvarez ,&nbsp;Elisa Martín-Merino","doi":"10.1016/j.bone.2024.117325","DOIUrl":"10.1016/j.bone.2024.117325","url":null,"abstract":"<div><h3>Background</h3><div>Discontinuation of anti-osteoporotic medications (AOM), except for bisphosphonates (BP), is not favorable for the bone, being especially negative for Prolia® (60 mg denosumab-DMAb). DMAb withdrawal leads to a rapid and significant increase in bone turnover markers, and to an important loss in bone mineral density, which has been associated with an increased risk of multiple vertebral fractures (MVF).</div></div><div><h3>Objective</h3><div>To assess the risk of MVF (≥2 VF) recorded at the same time) after discontinuation of different AOM.</div></div><div><h3>Methods</h3><div>A case-control analysis nested in a cohort of new users of DMAb, BP, Teriparatide (TPTD), Strontium Ranelate (SrRan), or selective estrogen receptor modulators (SERM), aged ≥18 years from 2011 to 2018 with ≥1 year of prior available data, was performed using the Pharmacoepidemiological Research Database for the Public Health System (BIFAP) in Spain. Cases were first MVF recorded after AOM initiation (index date). Up to 4 controls per case, matched on index date, age, sex, and location, were randomly selected among non-cases from the cohort. Adjusted conditional OR (AOR) and 95 % CI: between discontinuation of a given AOM (supply of the last prescription ended &gt;90 days before the index date) and occurrence of MVF was assessed compared with their current use and alternatively, with discontinuation of BP, among individuals who did not switch therapy in the study.</div></div><div><h3>Results</h3><div>A total of 532 incident cases of MVF were identified and matched to 2121 controls (86 % women; median age 73 years). AOR of MVF after DMAb discontinuation was 2.82 (1.73–4.60) compared with DMAb current use. No risk was seen for the other AOM. The AOR was highest between 3 and 9 months after discontinuation of denosumab (8.58; 3.98–18.48) and after &gt;1 year of cumulative use (5- and 11-times increased risk when discontinuing after 1–2 years and 2–5 years of use, respectively). Compared with BP discontinuers, discontinuation of DMAb (2.73, 1.66–4.50), TPTD (2.06, 1.09–3.88) and SrRan (1.93, 1.23–3.05) showed an increased risk of MVF; current use of DMAb showed no protective effect (1.44; 0.95–2.17).</div></div><div><h3>Conclusions</h3><div>Discontinuation of DMAb was associated with an immediate increased risk of MVF, especially after longest treatments compared with patients who continued therapy or discontinued BP. Although there were increased risks after discontinuation of other AOM in comparison with first- line therapy (BP), these were not found when the reference was current users. Confounding by indication cannot be discarded. Larger studies should investigate reasons for discontinuation and preventive retreatment options.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117325"},"PeriodicalIF":3.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634273","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}

{"title":"Tertiary hyperparathyroidism in two paediatric patients with X-linked hypophosphatemia during Burosumab treatment","authors":"Raja Padidela ,&nbsp;Lauren Rayner ,&nbsp;Annemieke M. Boot","doi":"10.1016/j.bone.2024.117324","DOIUrl":"10.1016/j.bone.2024.117324","url":null,"abstract":"<div><h3>Introduction</h3><div>Although secondary hyperparathyroidism is known in X-linked hypophosphatemia (XLH) patients receiving treatment, tertiary hyperparathyroidism with hypercalcemia is rare, especially in children. We report two paediatric XLH patients treated with Burosumab who developed this rare complication.</div></div><div><h3>Case descriptions</h3><div><strong>1:</strong> A female patient with XLH on conventional therapy (phosphate and active vitamin D) since one year of age was switched to Burosumab at 10 years. At 14 years of age, she developed tertiary hyperparathyroidism with hypercalcaemia. Burosumab was continued. Post-parathyroidectomy her hypercalcaemia resolved and 4 years post-surgery her calcium levels continue to remain normal.</div><div><strong>2:</strong> A female patient with XLH on conventional therapy since 4 months of age was switched to Burosumab at 4 years of age. At 7 years of age, she developed secondary hyperparathyroidism and within 6 months she developed tertiary hyperparathyroidism. Burosumab was discontinued at 7.5 years of age, and she was commenced on Cinacalcet but, hypercalcaemia failed to resolve. Post-parathyroidectomy her tertiary hyperparathyroidism resolved. However, within 2 weeks, PTH increased which normalised with Cinacalcet. Burosumab has been recommenced and she continues cinacalcet.</div></div><div><h3>Discussion</h3><div>The cause of tertiary hyperparathyroidism is not clear in these patients. Higher post-dose phosphate levels or a direct effect of <em>PHEX</em> mutation on the parathyroid gland could have triggered PTH secretion.</div></div><div><h3>Conclusion</h3><div>XLH patients treated with Burosumab can develop hyperparathyroidism and should be regularly monitored for the development of secondary and tertiary hyperparathyroidism.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117324"},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634354","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}

{"title":"Utilizing artificial intelligence to determine bone mineral density using spectral CT","authors":"Yali Li ,&nbsp;Dan Jin ,&nbsp;Yan Zhang ,&nbsp;Wenhuan Li ,&nbsp;Chenyu Jiang ,&nbsp;Ming Ni ,&nbsp;Nianxi Liao ,&nbsp;Huishu Yuan","doi":"10.1016/j.bone.2024.117321","DOIUrl":"10.1016/j.bone.2024.117321","url":null,"abstract":"<div><h3>Background</h3><div>Dual-energy computed tomography (DECT) has demonstrated the feasibility of using HAP-water to respond to BMD changes without requiring dedicated software or calibration. Artificial intelligence (AI) has been utilized for diagnosising osteoporosis in routine CT scans but has rarely been used in DECT. This study investigated the diagnostic performance of an AI system for osteoporosis screening using DECT images with reference quantitative CT (QCT).</div></div><div><h3>Methods</h3><div>This prospective study included 120 patients who underwent DECT and QCT scans from August to December 2023. Two convolutional neural networks, 3D RetinaNet and U-Net, were employed for automated vertebral body segmentation. The accuracy of the bone mineral density (BMD) measurement was assessed with relative measurement error (RME%). Linear regression and Bland–Altman analyses were performed to compare the BMD values between the AI and manual systems with those of the QCT. The diagnostic performance of the AI and manual systems for osteoporosis and low BMD was evaluated using receiver operating characteristic curve analysis.</div></div><div><h3>Results</h3><div>The overall mean RME% for the AI and manual systems were − 15.93 ± 12.05 % and − 25.47 ± 14.83 %, respectively. BMD measurements using the AI system achieved greater agreement with the QCT results than those using the manual system (R² = 0.973, 0.948, <em>p</em> &lt; 0.001; mean errors, 23.27, 35.71 mg/cm³; 95 % LoA, −9.72 to 56.26, −11.45 to 82.87 mg/cm³). The areas under the curve for the AI and manual systems were 0.979 and 0.933 for detecting osteoporosis and 0.980 and 0.991 for low BMD.</div></div><div><h3>Conclusion</h3><div>This AI system could achieve relatively high accuracy for automated BMD measurement on DECT scans, providing great potential for the follow-up of BMD in osteoporosis screening.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117321"},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634332","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}

{"title":"Exposure to fluoride and risk of primary bone cancer: A systematic review","authors":"Natalie Hajduga ,&nbsp;Murali Perumbakkam Subramanian ,&nbsp;Hannah Brown ,&nbsp;Richard McNally ,&nbsp;Vida Zohoori ,&nbsp;Vikki Rand","doi":"10.1016/j.bone.2024.117320","DOIUrl":"10.1016/j.bone.2024.117320","url":null,"abstract":"<div><div>Fluoride has long been considered essential in the prevention of dental caries, however, its relationship with bone cancer remains unclear. With little improvements in survival from primary bone cancers, it is important to understand the underlying drivers. The focus of this systematic review was, therefore, to assess the association between fluoride exposure and the development of primary bone cancer. The review was conducted as per the PRISMA guidelines and was registered on PROSPERO (CRD42021296109) with a search cut-off of March 2024. In total, 14 studies, involving 8680 participants across all age groups, were identified examining the effects of fluoride exposure on humans investigated for primary bone cancer. Of the 14 studies, only two reported a positive association between fluoride and primary bone cancer. One study including 88 participants reported a positive association between water fluoridation and osteosarcoma development (in young males between 0 and 20 years of age), and the second study, with an unreported number of participants, reported this positive association with bone cancers in males. No association between fluoridation and bone cancer development was reported in the remaining studies. Across all 14 studies, data was presented in a narrative synthesis with subgroup analysis conducted on study design, age, sex, fluoride level and quality score. Both studies reporting a positive association between fluoride and bone cancer identified this association in males, however, both studies concluded that further research is needed. Here we report the most comprehensive systematic review to date examining associations between fluoride exposure and primary bone cancer. We also highlight some of the methodological limitations of some studies, and identify the need, and opportunity, to conduct a large, prospective study to address this and other health issues associated with fluoride.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117320"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607624","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}

{"title":"Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis","authors":"Wanying Jiang ,&nbsp;Xinyi Ma ,&nbsp;Bin Li ,&nbsp;Tianle Jiang ,&nbsp;Haopu Jiang ,&nbsp;Wenxia Chen ,&nbsp;Jia Gao ,&nbsp;Yixin Mao ,&nbsp;Xiaoyu Sun ,&nbsp;Zhou Ye ,&nbsp;Shufan Zhao ,&nbsp;Shengbin Huang ,&nbsp;Yang Chen","doi":"10.1016/j.bone.2024.117322","DOIUrl":"10.1016/j.bone.2024.117322","url":null,"abstract":"<div><div>Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca²⁺. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP.</div></div><div><h3>Lay summary</h3><div>This study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117322"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607626","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}

{"title":"Extracellular vesicles from mouse bone marrow macrophages-derived osteoclasts treated with zoledronic acid contain miR-146a-5p and miR-322-3p, which inhibit osteoclast function","authors":"Sakura Minami ,&nbsp;Yasuyuki Fujii ,&nbsp;Yusuke Yoshioka ,&nbsp;Ayano Hatori ,&nbsp;Kotaro Kaneko ,&nbsp;Takahiro Ochiya ,&nbsp;Daichi Chikazu","doi":"10.1016/j.bone.2024.117323","DOIUrl":"10.1016/j.bone.2024.117323","url":null,"abstract":"<div><div>Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Then, extracellular vesicles (EVs) carry various signaling molecules, such as mRNAs, microRNAs (miRNAs), and proteins, and have attracted attention as intercellular communication tools. Recently, the role of EVs in communication between osteoclasts and surrounding bone cells has been confirmed. This study aimed to elucidate the effects of EVs derived from osteoclasts treated with zoledronic acid (ZA), one of the BPs on osteoclast function. EVs were isolated by ultracentrifugation of the culture supernatant of osteoclasts treated with ZA, and miRNAs were extracted from these EVs. Tartrate-resistant acid phosphatase staining of the ZA treated osteoclasts showed reduced osteoclastogenesis. In addition, pit assay showed that ZA significantly decreased the bone resorption capacity of osteoclasts. miRNA-seq analysis identified 11 upregulated and 5 downregulated differentially expressed genes (DEGs) in the miRNA of EVs derived from ZA-treated osteoclasts compared to EVs derived from osteoclasts not treated with ZA. qRT-PCR analysis confirmed the amount of these specific miRNAs, with miR-146a-5p, and miR-322-3p being significantly upregulated by ZA. Overexpression of miR-146a-5p in osteoclasts inhibited osteoclastogenesis and decreased the mRNA expression of osteoclast markers. In addition, <em>Traf6</em> was identified as a candidate target gene of miR-146a-5p in several miRNA databases. Indeed, the overexpression of miR-146a-5p decreased the expression level of <em>Traf6</em> in osteoclasts. Additionally, overexpression of miR-322-3p in the pre-osteoblast, MC3T3-E1 cells, resulted in a significant increase in the mRNA expression levels of <em>Sp7</em>. Our data indicate that BPs attenuate osteoclastogenesis by simultaneously altering the characteristics of osteoclast-derived EVs. Overexpression of miR-146a-5p and miR-322-3p influences osteoclast differentiation, and <em>Traf6</em> is a target gene of miR-146a-5p. On the other hand, Overexpression of miR-322-3p affects osteoblast differentiation. We suggest that ZA-treated osteoclast-derived EVs may play an important role in osteoclast function and bone resorption.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117323"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607625","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}

{"title":"Biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB for skull repair","authors":"Zihao Zhan ,&nbsp;Ran Li ,&nbsp;Yiang Wu ,&nbsp;Xiaotian Shen ,&nbsp;Dongming Fu ,&nbsp;Hao Han ,&nbsp;Pengrui Jing ,&nbsp;Bin Li ,&nbsp;Fengxuan Han ,&nbsp;Bin Meng","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":"190 ","pages":"Article 117315"},"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}

{"title":"Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair","authors":"Daniel Kronenberg ,&nbsp;Melanie Brand ,&nbsp;Jens Everding ,&nbsp;Louisa Wendler ,&nbsp;Eric Kieselhorst ,&nbsp;Melanie Timmen ,&nbsp;Michael D. Hülskamp ,&nbsp;Richard Stange","doi":"10.1016/j.bone.2024.117318","DOIUrl":"10.1016/j.bone.2024.117318","url":null,"abstract":"<div><div>Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways. Among these, BMP-2 was identified as the key signaling protein responsible for this effect, as its expression was significantly upregulated during osteoblast differentiation. Moreover, integrin α2 deficiency led to earlier and elevated BMP-2 secretion at the cell surface during osteogenesis, which promoted accelerated osteoblast differentiation. This phenomenon likely contributes to enhanced matrix production in aging animals, providing a protective effect against osteoporosis.</div><div>To explore the broader implications of this phenotype, we utilized a fracture healing model. In integrin α2-deficient 12 weeks old female mice, elevated serum levels of BMP-2 were detected during the early stages of fracture repair. This upregulation of BMP signaling within the fracture callus accelerated the healing process, resulting in faster formation and mineralization of the cartilaginous callus. Additionally, the elevated BMP-2 levels facilitated earlier differentiation of chondrocytic cells, evidenced by the premature appearance of collagen type II- and type X-positive cells during endochondral ossification. Despite the accelerated healing, the overall biomechanical integrity of the repaired fractures remained uncompromised.</div><div>Thus, the modulation of integrin α2β1 presents a promising therapeutic target for enhancing fracture repair by regulating BMP-2 signaling in a physiologically relevant manner.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117318"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585208","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}