Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor (IR) selectively in chondrocytes (CartIR2/2) had no discernable differences in total femoral length compared to control littermates. However, CartIR2/2 mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor (IGF)-1R mRNA and protein levels. Subsequently, IGF-1 induced phosphorylation of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR2/2 mice when compared with that of the control littermates, which was associated with upregulation of tuberous sclerosis complex 2 (TSC2). These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.

作者： 刊期： 2014年第02期

Cone-beam computed tomography (CBCT) has been recently used to analyse trabecular bone structure around dental implants. To validate the use of CBCT for three-dimensional (3D) peri-implant trabecular bone morphometry by comparing it to two-dimensional (2D) histology, 36 alveolar bone samples (with implants n527 vs. without implants n59) from six mongrel dogs, were scanned ex vivo using a high-resolution (80 mm) CBCT. After scanning, all samples were decalcified and then sectioned into thin histological sections (,6 mm) to obtain high contrast 2D images. By using CTAn imaging software, bone morphometric parameters including trabecular number (Tb.N), thickness (Tb.Th), separation (Tb.Sp) and bone volume fraction (BV/TV) were examined on both CBCT and corresponding histological images. Higher Tb.Th and Tb.Sp, lower BV/TV and Tb.N were found on CBCT images (P,0.001). Both measurements on the peri-implant trabecular bone structure showed moderate to high correlation (r50.65-0.85). The Bland-Altman plots showed strongest agreement for Tb.Th followed by Tb.Sp, Tb.N and BV/TV, regardless of the presence of implants. The current findings support the assumption that peri-implant trabecular bone structures based on high-resolution CBCT measurements are representative for the underlying histological bone characteristics, indicating a potential clinical diagnostic use of CBCT-based peri-implant bone morphometric characterisation.

作者： 刊期： 2014年第02期

Osteoporotic fractures are a major public health problem worldwide, but incidence varies greatly across racial groups and geographic regions. Recent work suggests that the incidence of osteoporotic fracture is rising among Asian populations. Studies comparing areal bone mineral density and fracture across races generally indicate lower bone mineral density in Asian individuals including the Chinese, but this does not reflect their relatively low risk of non-vertebral fractures. In contrast, the Chinese have relatively high vertebral fracture rates similar to that of Caucasians. The paradoxically low risk for some types of fractures among the Chinese despite their low areal bone mineral density has been elucidated in part by recent advances in skeletal imaging. New techniques for assessing bone quality non-invasively demonstrate that the Chinese compensate for smaller bone size by differences in hip geometry and microstructural skeletal organization. Studies evaluating factors influencing racial differences in bone remodeling, as well as bone acquisition and loss, may further elucidate racial variation in bone microstructure. Advances in understanding the microstructure of the Chinese skeleton have not only helped to explain the epidemiology of fracture in the Chinese, but may also provide insight into the epidemiology of fracture in other races as well.

作者： 刊期： 2014年第02期

Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh2/2 mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh2/2 mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh2/2;Gli32/2 embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.

作者： 刊期： 2014年第02期

Locking plate fixation is being widely applied for fixation of forearm fractures and has many potential advantages, such as fixed angle fixation and improved construct stability, especially in osteoporotic bone. Biomechanical data comparing locking devices to commonly used Low Contact Dynamic Compression (LCDCP) plates for the fixation of forearm fractures has been lacking. The purpose of this study was to compare the fixation stability of a 3.5-mm unicortical locked plate with bicortical non-locked LCDCP plates. Six matched pairs of fresh frozen cadaveric forearms were randomly assigned to unicortical locked and bicortical unlocked groups. Non-destructive four-point bending and torsional test was performed on the ulna and radius separately, using a servohydraulic testing system to obtain construct stiffness of the intact specimens and specimens after osteotomy and plating. The specimens were then loaded to failure to test the fixation strength. The locked unicortical fixation showed significantly higher bending stiffness than the unlocked bicortical fixation, but with significantly lower stiffness and strength in torsion. Fixation strength was comparable between the two groups under bending, but significantly greater in the bicortical non-locked group under torsion. Findings from this study suggest that postoperative rehabilitation protocols may need modification to limit torsional loading in the early stage when using locked unicortical fixation. The study also points out the potential advantage of a hybrid fixation that combines locked unicortical and unlocked bicortical screws.

作者： 刊期： 2014年第02期

作者： 刊期： 2014年第02期

Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D (1,25(OH)2D) by functioning as a vitamin D response element-binding protein (VDRE-BP). hnRNPC acts a tetramer of hnRNPC1 (huC1) and hnRNPC2 (huC2), and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25(OH)2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25(OH)2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a‘‘self-cleaving’’ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25(OH)2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.

作者： 刊期： 2014年第02期

Osteoarthritis (OA) is a common joint degenerative disease affecting the whole joint structure, including articular cartilage, subchondral bone and synovial tissue. Although extensive work has been done in recent years to explore the molecular mechanism underlying this disease, the pathogenesis of OA is still poorly understood and currently, there is no effective disease-modifying treatment for OA. Recently, both in vitro and in vivo studies suggest that confirmed (TGF-b)/SMAD pathway plays a critical role during OA development. This short review will focus on the function and signaling mechanisms of TGF-b/SMAD pathway in articular chondrocytes, mesenchymal progenitor cells of subchondral bone and synovial lining cells during OA development.

作者： 刊期： 2014年第02期