Bone最新文献

Endochondral ossification (EO) is a pivotal process during fracture healing and traumatic heterotopic ossification (HO), involving the cartilaginous matrix synthesis and mineralization. Unlike the extracellular matrix, the hyaluronan (HA)-rich pericellular matrix (PCM) directly envelops chondrocytes, serving as the frontline for extracellular signal reception and undergoing dynamic remodeling. Pentraxin 3 (PTX3), a secreted glycoprotein, facilitates HA matrix assembly and remodeling. However, it remains unclear whether PTX3 affects EO by regulating HA-rich PCM assembly of chondrocytes, thereby impacting fracture healing and traumatic HO. This study demonstrates that PTX3 deficiency impairs fracture healing and inhibits traumatic HO, but dose not affect growth plate development in mice. PTX3 expression is up-regulated during chondrocyte matrix synthesis and maturation and is localized in the HA-rich PCM. PTX3 promotes the assembly of HA-rich PCM in a serum- and TSG6-dependent manner, fostering CD44 receptor clustering, activating the FAK/AKT signaling pathway, and promoting chondrocyte matrix synthesis and maturation. Local injection of PTX3/TSG6 matrix protein mixture effectively promotes fracture healing in mice. In conclusion, PTX3-assembled HA-rich PCM promotes chondrocyte matrix synthesis and maturation via CD44/FAK/AKT signaling. This mechanism facilitates EO during fracture healing and traumatic HO in mice.

Induced membrane technique (IMT) is a new method for repairing segmental bone defects. However, the mechanism of its defect repair is not clear. In recent years, several studies have gradually indicated that ferroptosis is closely related to bone remodeling. Therefore, this study mainly explored the impact of NRF2-mediated osteoblast anti-ferroptosis on bone mineralization within the induced membrane. Male Sprague-Dawley rats aged 12-14 weeks were randomly divided into four groups (n = 12): Model group, DMF (NRF2 agonist) group, ML385 (NRF2 inhibitor) group and Sham group. Except for Sham group, an IMT model of the right femur was established in all other groups. After 4 weeks and 8 weeks of treatment with DMF and ML385, compared to Model group, DMF group showed significantly higher levels of bone volume fraction (BV/TV), osteogenic factors and NRF2/ARE pathway-related factors (NRF2, GPX4, HO-1 and SLC7A11), while ferroptosis-related indicators (total iron, 4-HNE and MDA) were significantly lower. Conversely, ML385 group exhibited significantly higher ferroptosis-related indicators and lower levels of NRF2/ARE pathway-related factors and osteogenesis. In vitro, erastin could induce ferroptosis in osteoblasts. Compared to Erastin group, Erastin+oe-NRF2 (NRF2 overexpression) group showed significantly increased cell viability, mineralization ability, and levels of NRF2/ARE pathway-related factors, along with reduced ferroptosis effects. However, Erastin+si-NRF2 (NRF2 small interfering) group displayed enhanced ferroptosis effects and significantly reduced cell viability, mineralization ability, and levels of NRF2/ARE pathway-related factors. In conclusion, in the bone grafting area of the induced membrane, there existed ferroptosis caused by iron overload. Activating the anti-ferroptosis effect of osteoblasts mediated by the NRF2/ARE signaling cascade could promote growth and mineralization of bone grafts within the induced membrane.

Metabolic pathways exhibit fluctuating activities during bone and dental loss and defects, suggesting a regulated metabolic plasticity. Skeletal remodeling is an energy-demanding process related to altered metabolic activities. These metabolic changes are frequently associated with epigenetic modifications, including variations in the expression or activity of enzymes modified through epigenetic mechanisms, which directly or indirectly impact cellular metabolism. Metabolic reprogramming driven by bone and dental conditions alters the epigenetic landscape by modulating the activities of DNA and histone modification enzymes at the metabolite level. Epigenetic mechanisms modulate the expression of metabolic genes, consequently influencing the metabolome. The interplay between epigenetics and metabolomics is crucial in maintaining bone and dental homeostasis by preserving cell proliferation and pluripotency. This review, therefore, aims to examine the effects of metabolic reprogramming in bone and dental-related cells on the regulation of epigenetic modifications, particularly acetylation, methylation, and lactylation. We also discuss the effects of chromatin-modifying enzymes on metabolism and the potential therapeutic benefits of dietary compounds as epigenetic modulators. In this review, we highlight the inconsistencies in current research findings and suggest potential approaches to translate fundamental insights into clinical treatments for bone and tooth diseases.

Bone sialoprotein (Ibsp/BSP) is a bone-associated extracellular matrix protein. Ibsp knockout (Ibsp^-/-) mice exhibit defective alveolar bone formation, mineralization, and healing. We hypothesized BSP would rescue defective alveolar bone healing in a molar extraction model in Ibsp^-/- mice. Collagen gel with or without native rat BSP (nBSP) or recombinant rat BSP (rBSP) was delivered to sockets after first maxillary molar extraction in Ibsp^-/- and wild-type (WT) mice. Tissues were harvested 0, 1, 2, 7, and 14 days post-procedure (dpp) and analyzed by micro-computed tomography, histology, and immunohistochemistry (IHC). Histology and IHC demonstrated that collagen and BSP were retained within sockets. At 14 dpp, both bone volume fraction (BV/TV) and bone mineral density (BMD) were increased by both nBSP (over 50 %) and rBSP (over 60 %), compared to collagen alone in Ibsp^-/- mice. In WT alveolar bone, BV/TV and BMD were also increased by nBSP (over 30 %) and rBSP (over 60 %) compared to collagen controls. Gene expression analyses revealed few changes from delivery of nBSP, while addition of rBSP resulted in regulation of cell signaling, ECM, mineralization, and osteoblast/osteoclast-associated genes. Exogenous BSP rescued alveolar bone healing defects in Ibsp^-/- mice and enhanced bone healing in WT mice. Despite both forms of BSP improving bone healing, the substantial differences in how they regulate gene expression suggests that exogenous BSP acts in a complex, multifunctional manner to promote bone healing. These results support BSP as a novel approach to improve the quantity and quality of new bone in socket healing.

Obesogenic feeding can affect systemic metabolism and impact bone health and microarchitecture, but the findings of published studies often appear contradictory. This study aimed to compare the effects of a medium-fat/high-sugar (MF/HS) and a high-fat/high-fructose (HF/Fr) diet on the femora of weanling male Wistar rats, examining bone mineral content and density (BMC, BMD), cortical and cancellous bone microarchitecture and the cell populations within bone. Furthermore, we explored the correlations between circulating bone-targeting factors (in particular leptin, adiponectin and insulin) and bone parameters. Rats were assigned to one of three dietary groups (control: CON; MF/HS: OB1; HF/Fr: OB2; n = 12 each) for 17 weeks. Right-hand side femora were subjected to densitometry to measure BMC and BMD, and micro-computed tomography (μCT) was utilised to assess cortical and cancellous bone. Osteoblast (N.Ob), osteoclast (N.Oc), adipocyte (N.Ad) and chondrocyte numbers (N.Ch) were quantified histomorphometrically. Diet OB1 was largely beneficial to bone, while diet OB2 exerted detrimental effects on BMC, BMD, bone microarchitecture and bone cell populations. In cortical bone, N.Ob was positively correlated with BMD, cortical area and serum leptin. In cancellous bone, N.Ob was positively correlated with serum leptin and BMD, while N.Oc was negatively correlated with serum leptin. Overall, these findings support a role for endogenous circulating leptin in promoting bone formation. We conclude that the impact of different obesogenic diets may be driven by individual dietary effects on circulating factors, which may partly explain the contradictory reports in existing literature on the impact of HF and HS diets on bone.

ACL injuries commonly lead to post-traumatic osteoarthritis (PTOA), but the underlying mechanism is not well-understood. One theorized mechanism is pathological bone remodelling following an ACL tear, for which high-resolution peripheral quantitative computed tomography (HR-pQCT) is uniquely positioned to investigate in vivo in humans. In this study, we longitudinally investigate the one-year changes in periarticular bone density and microarchitecture in the human knee following an ACL tear and reconstructive surgery using data sampled from an on-going observational cohort study. We reduce the number of individual microarchitectural parameters using factor analysis and model one-year changes with mixed-effects models, adjusting for the effects of age, sex, meniscus status, and the baseline microarchitectural state. We find significant evidence of persistent bone density losses one year after both injury and surgery. We also observe significant increases in trabecular separation post-injury, indicating significant structural degradation, and significant increases in subchondral bone plate density post-surgery, a sign of early stiffening. Finally, we observe minimal significant contrasts for the effects of age, sex, and meniscus status, while we observe that the state of the microarchitecture at baseline has significant and varied effects on the subsequent changes, suggesting that the influence of PTOA risk factors on post-injury and post-surgery bone changes may be mediated through the state of the periarticular microarchitecture at injury and/or at surgery. In summary, we found that degradation of periarticular bone microarchitecture was observed post-injury, densification of the subchondral bone plate was observed post-surgery, and the state of the bone microarchitecture at baseline may mediate the influence of PTOA risk factors on post-injury microarchitectural adaptations.

Objectives: Alcoholic bone disease has been recognized in contemporary literature as a systemic effect of chronic ethanol consumption. However, evidence about the specific influence of alcoholic liver cirrhosis (ALC) on mandible bone quality is scarce. The aim of this study was to explore microstructural, compositional, cellular, and mechanical properties of the mandible in ALC individuals compared with a healthy control group.

Materials and methods: Mandible bone cores of mаle individuаls with ALC (n = 6; age: 70.8 ± 2.5 yeаrs) and age-matched healthy controls (n = 11; age: 71.5 ± 3.8 yeаrs) were obtаined postmortem during аutopsy from the edentulous аlveolаr bone in the mandibular first molаr region аnd the mаndibulаr аngulus region of each individual. Micro-computed tomogrаphy wаs used to аssess bone microstructure. Analyses based on quаntitаtive bаckscаttered electron microscopy included the characterization of osteon morphology, osteocyte lаcunаr properties, and bone mаtrix minerаlizаtion. Composition of bone minerаl аnd collаgen phаses was assessed by Rаmаn spectroscopy. Histomorphometry wаs used to determine cellulаr аnd tissue chаrаcteristics of bone specimens. Vickers microhardness test was used to evaluate cortical bone mechanical properties.

Results: The ALC group showed higher closed cortical porosity (volume of pores thаt do not communicаte with the sаmple surfаce) (p = 0.003) and smaller lacunar area in the trabecular bone of the molar region (p = 0.002) compared with the Control group. The trabecular bone of the angulus region showed lower osteoclast number (p = 0.032) in the ALC group. There were higher carbonate content in the buccal cortex of the molar region (p = 0.008) and lower calcium content in the trabecular bone of the angulus region (p = 0.042) in the ALC group. The cortical bone showed inferior mechanical properties in the ALC cortical bony sites (p < 0.001), except for the buccal cortex of the molar region (p = 0.063). There was no significant difference in cortical thickness between the groups.

Conclusions: Bone quality is differentially altered in ALC in two bony sites and compartments of the mandible, which leads to impaired mechanical properties.

Clinical relevance: Altered mandible bone tissue characteristics in patients with ALC should be considered by dental medicine professionals prior to oral interventions in these patients. Knowledge about mandible bone quality alterations in ALC is valuable for determining diagnosis, treatment plan, indications for oral rehabilitation procedures, and follow-up procedures for this group of patients.

Background: Differences in bone metabolism between patients with adrenal Cushing's syndrome (ACS) and Cushing's disease (CD) have been noted, but the impact of steroid hormones on bone metabolism remains underexplored. The purpose of this study is to explore the differences in bone metabolism between the two subtypes of Cushing's syndrome and the correlation between hormones synthesized by the adrenal reticulum and bone metabolism.

Method: This retrospective study included 75 premenopausal women, consisting of 33 patients with CD and 42 patients with ACS. The clinical characteristics, laboratory examination and bone metabolism differences between the two groups were analyzed. Then, 16 patients with ACS and 12 patients with CD underwent comparison of blood steroid hormone levels. Additionally, the relationship between bone mineral density (BMD) values and steroid hormone variables was analyzed.

Results: The serum and urinary cortisol and serum ACTH concentrations were significantly higher in patients with CD compared to those with ACS. Conversely, lumbar and femoral BMD were lower, and osteocalcin (OC) levels were elevated in the ACS group. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) had a significant positive correlation with Z-score in lumbar spine in both CD and ACS group. However, Z-score in femoral neck had a significant positive correlation with DHEA and DHEAS only in the ACS group.

Conclusion: Bone loss is more pronounced in ACS than in CD, despite higher cortisol levels in CD patients. High levels of hormones synthesized by the adrenal reticulum might be protective for bone density in premenopausal women with hypercortisolism.