Department of Orthopedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Department of Orthopedic Surgery, Cangzhou People's Hospital, Cangzhou, 061000, Hebei, China.
J Orthop Surg Res. 2023 Jul 24;18(1):526. doi: 10.1186/s13018-023-04019-6.
Patellar instability (PI) at an early age is believed closely correlated with bone loss in the development of the femoral trochlea and can cause trochlear dysplasia. However, the molecular mechanism of PI-induced bone loss has not been established. The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway plays an important role in bone development by regulating the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL). The aim of this study was to explore the association of JAK1/STAT3 signaling to PI-induced subchondral bone loss in the femoral trochlea.
Four-week-old male C57BL/6 mice were randomly divided into two groups (n = 50/group). Mice in the experimental group underwent surgery to induce PI. Distal femurs were collected 2 and 4 weeks after surgery (n = 25 knees/each time point, each group). Microcomputed tomography and histological observations were performed to investigate the morphology of the femoral trochlea and changes in bone mass. qPCR, western blot, and immunohistochemistry analyses were performed to evaluate the expression of JAK1, STAT3, RANKL, and OPG in subchondral bone. A t test was performed for the statistical analysis; a P value < 0.05 was considered to be statistically significant.
In the experimental group, subchondral bone loss in the femoral trochlea was observed two and four weeks after PI; morphological changes, such as a flatter trochlear groove and an increased sulcus angle, were observed in the femoral trochlea; qPCR, western blot, and immunohistochemistry analyses showed higher expression of JAK1, STAT3, and RANKL and lower expression of OPG (P < 0.05).
PI-induced subchondral bone loss in the femoral trochlea and resulted in trochlear dysplasia in growing mice. This bone loss is associated with activation of the JAK1/STAT3 signaling pathway, which weakens the function of osteoblasts and stimulates both formation and function of osteoclasts.
人们认为，幼年时髌骨不稳定（PI）与股骨滑车发育过程中的骨丢失密切相关，并可导致滑车发育不良。然而，PI 引起的骨丢失的分子机制尚未建立。Janus 激酶（JAK）/信号转导子和转录激活子（STAT）信号通路通过调节护骨素（OPG）和核因子κB 受体激活剂配体（RANKL）的表达，在骨骼发育中发挥重要作用。本研究旨在探讨 JAK1/STAT3 信号通路与 PI 诱导的股骨滑车下骨丢失的关系。
将 4 周龄雄性 C57BL/6 小鼠随机分为两组（每组 n=50）。实验组行手术诱导 PI。术后 2 周和 4 周（每组 n=25 个膝关节/每个时间点）采集远端股骨。进行 microCT 和组织学观察，以研究股骨滑车的形态和骨量变化。进行 qPCR、western blot 和免疫组化分析，以评估软骨下骨中 JAK1、STAT3、RANKL 和 OPG 的表达。采用 t 检验进行统计学分析；P 值<0.05 为差异有统计学意义。
实验组术后 2 周和 4 周观察到股骨滑车下软骨下骨丢失；股骨滑车出现形态学改变，如滑车沟变平、滑车沟角增大；qPCR、western blot 和免疫组化分析显示 JAK1、STAT3 和 RANKL 表达升高，OPG 表达降低（P<0.05）。
PI 诱导生长中小鼠股骨滑车下软骨下骨丢失并导致滑车发育不良。这种骨丢失与 JAK1/STAT3 信号通路的激活有关，该通路削弱了成骨细胞的功能，并刺激破骨细胞的形成和功能。
