Abstract:

Objective: To investigate the effects of hypoxia inducible factor-1α(HIF-1α) on the development of articular cartilage and subchondral bone in mice via regulating the formation and activity of osteoclasts. Methods: Mice with specific knockout of HIF-1α were constructed. The morphological structures of cartilage and subchondral bone of the mandibular condyle, femoral head and the growth plate of femur epiphysis were compared between the littermate control (HIF-1α^f/f; Ctsk-cre^-) mice group and conditional knockout (cKO) (HIF-1α^f/f; Ctsk-cre⁺) mice group by the micro-CT evaluation and histological staining. Results: At the ages of five and eight weeks, compared with the control group, the hypertrophic cartilage layer of femoral head became thinner and the chondrocytes arranged more irregular in cKO mice group. The growth plate of femoral epiphysis and morphological structure of the subchondral bone layers did not change significantly. At 10-week-old, micro-CT scan results showed that the condyle articular surface of the cKO group lost its original convex structure, showing a horizontal concave shape, with increased anterior-posterior diameters and proximal-distal diameters, and decreased width and length of the condyle. The cartilage layers were disordered, and the fibrocartilaginous layer became markedly thicker. Knockout of HIF-1α affects on the formation and function of osteoclasts in the subchondral region of condyle, femoral head and epiphyseal growth plate, and the femur in the 8-week group is more affected than the 5-week group. And compared to femur, the effects of HIF-1α knockout on osteoclasts in the subcondral bone region of mandibular condyle were more obvious in each time group. Conclusion: During the development of cartilage and subchondral bone of mouse femur and mandibular condyle, HIF-1α can regulate the formation and the activity of osteoclasts to maintain the remodeling and morphology of cartilage and subchondral bone. This effect on the condylar cartilage and subchondral bone is more pronounced than that of femur.

Key words: hypoxia inducible factor-1α, osteoclast, cartilage, subchondral bone

摘要：

目的 ：研究低氧诱导因子-1α（hypoxia inducible factor-1α，HIF-1α）调控破骨细胞形成和活性在小鼠关节软骨和软骨下骨发育中的影响。方法： 构建破骨细胞内特异性敲除HIF-1α的模式鼠；通过micro-CT评估、组织学染色观察同窝对照鼠（HIF-1α^f/f; Ctsk-cre^-）和条件性敲除（conditional knockout，cKO）鼠（HIF-1α^f/f; Ctsk-cre⁺）下颌骨髁突、股骨头和股骨骺端生长板的软骨和软骨下骨形态结构。结果： 在5周龄和8周龄时，组织学染色发现，相比同窝对照鼠，cKO鼠股骨头的肥大软骨层变薄，细胞排列欠规则；股骨骺端生长板及软骨下骨区形态结构无明显变化；在10周龄时，micro-CT扫描结果表明，髁突关节面失去原有凸形结构，呈水平凹形，前后径及近远中径增大，髁突宽度、长度缩短，软骨层紊乱，纤维软骨层明显变厚。HIF-1α敲除对髁突、股骨头和骺端生长板软骨下骨区破骨细胞的形成和功能均有影响，8周龄组的股骨影响较5周龄组明显；较股骨组， HIF-1α敲除对下颌骨髁突软骨下骨区破骨细胞的影响在各时间组均较明显。结论： 在小鼠股骨和下颌骨软骨、软骨下骨发育过程中，HIF-1α可调控破骨细胞的形成和破骨活性，进而维持软骨及软骨下骨的改建和形态；HIF-1α的调控作用对髁突软骨和软骨下骨发育的影响较股骨更为明低。

关键词: 低氧诱导因子-1α, 破骨细胞, 软骨, 软骨下骨

CLC Number: 

• R782