School of Stomatology, Zhejiang Chinese Medicine University, Hang Zhou 310054, China; State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, 710032 Xi'an, China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, 710032 Xi'an, China.
Arch Oral Biol. 2022 Mar;135:105365. doi: 10.1016/j.archoralbio.2022.105365. Epub 2022 Feb 2.
The aim of this study was to demonstrate the biological function of Semaphorin 4D (Sema4D)/Plexin-B1 in the bone formation features of osteoblasts in early-stage temporomandibular joint (TMJ) osteoarthritis.
Sema4D/Plexin-B1, expressed by osteoclasts/osteoblasts, plays a balancing role in bone formation and resorption. However, previous studies have mainly focused on bone resorption by osteoclasts in early-stage osteoarthritis. This study used our reported experimental unilateral anterior crossbite (UAC) mouse model to explore subchondral bone changes, which were assessed by micro-CT analysis. The changes in osteoblasts were investigated after the inhibition of Sema4D by BMA-12 injection with the detection of bone formation-related markers. A Transwell migration assay was performed to reveal the specific impact of Sema4D on osteoblasts in vitro.
The data demonstrated that subchondral bone loss in early-stage TMJ osteoarthritis was accompanied by the upregulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D levels could inhibit subchondral bone loss and cartilage degeneration in early-stage TMJ osteoarthritis. In vitro, the results revealed that Sema4D could reduce the expression of osteocalcin and alkaline phosphatase and increase the migrating capability of Plexin-B1-positive osteoblasts.
Our results revealed that elevated Sema4D expression in early-stage TMJ osteoarthritis might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in early-stage osteoarthritis represents a promising strategy for new therapeutic approaches to osteoarthritis.
本研究旨在展示信号素 4D（Sema4D）/神经纤毛蛋白受体 B1（Plexin-B1）在早期颞下颌关节（TMJ）骨关节炎成骨细胞骨形成特征中的生物学功能。
破骨细胞/成骨细胞表达的 Sema4D/Plexin-B1 在骨形成和吸收中发挥着平衡作用。然而，之前的研究主要集中在早期骨关节炎中破骨细胞的骨吸收上。本研究使用我们报道的实验性单侧前牙交叉咬合（UAC）小鼠模型来研究软骨下骨的变化，通过微 CT 分析进行评估。在注射 BMA-12 抑制 Sema4D 后，检测骨形成相关标志物，研究成骨细胞的变化。进行 Transwell 迁移实验以揭示 Sema4D 对体外成骨细胞的具体影响。
数据表明，早期 TMJ 骨关节炎软骨下骨丢失伴随着软骨和软骨下骨中 Sema4D 的上调表达和软骨下骨中 Plexin-B1 的上调表达。降低 Sema4D 水平可以抑制早期 TMJ 骨关节炎的软骨下骨丢失和软骨退化。体外结果显示，Sema4D 可以降低骨钙素和碱性磷酸酶的表达，并增加 Plexin-B1 阳性成骨细胞的迁移能力。
我们的结果表明，早期 TMJ 骨关节炎中 Sema4D 的表达升高可能通过与成骨细胞表达的 Plexin-B1 结合，降低软骨下骨中成骨细胞的骨形成活性。抑制早期骨关节炎中的 Sema4D/Plexin-B1 信号通路可能是骨关节炎新治疗方法的一种有前途的策略。
