Parathyroid hormone ameliorates temporomandibular joint osteoarthritic-like changes related to age
Parathyroid hormone ameliorates temporomandibular joint osteoarthritic-like changes related to age
复制标题
甲状旁腺激素可改善与年龄相关的颞下颌关节骨关节炎样变化
DOI：
10.1111/cpr.12755
复制
发表时间：
2020-04-01
影响因子：
8.5
通讯作者：
Zhou, Xuedong
中科院分区：
文献类型：
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作者：
Cui, Chen;Zheng, Liwei;Zhou, Xuedong
目的 衰老可能是颞下颌关节骨关节炎 (TMJ OA) 进展的一个促成因素，但其发病机制和潜在的治疗策略尚未得到全面研究。 材料和方法 我们生成衰老小鼠模型（45 周和 60 周；12 周小鼠作为对照），并对 45 周小鼠间歇注射甲状旁腺激素 (PTH(1-34)) 或载体 4 周。通过 microCT、组织学和免疫染色对 TMJ 的软骨和软骨下骨进行分析。采用Western blot、qRT-PCR、ChIP、ELISA和免疫组化分析研究PTH(1-34)的功能机制。结果我们在衰老小鼠中发现了明显的OA样表型。 PTH 治疗可以通过激活骨重塑来改善软骨下骨的退行性变化并改善骨微结构。此外，PTH抑制Smad3的磷酸化水平，Smad3可以与p16(ink4a)基因启动子区结合，导致衰老细胞积累减少，骨髓间充质干细胞(MSCs)细胞增殖增加。 ELISA 还显示 PTH 治疗后衰老小鼠的特异性衰老相关分泌表型 (SASP) 水平有所缓解。 结论 总之，PTH 可能通过抑制 p16(ink4a) 减少软骨下骨中衰老细胞的积累，并改善骨髓微环境以促进骨重塑过程，表明 PTH 给药可能是年龄相关性 TMJ OA 的潜在预防和治疗方法。
Objectives Ageing could be a contributing factor to the progression of temporomandibular joint osteoarthritis (TMJ OA), whereas its pathogenesis and potential therapeutic strategy have not been comprehensively investigated.Materials and methods We generated ageing mouse models (45-week and 60-week; 12-week mice as control) and intermittently injected 45-week mice with parathyroid hormone (PTH(1-34)) or vehicle for 4 weeks. Cartilage and subchondral bone of TMJ were analysed by microCT, histological and immunostaining. Western blot, qRT-PCR, ChIP, ELISA and immunohistochemical analysis were utilized to examination the mechanism of PTH(1-34)'s function.Results We showed apparent OA-like phenotypes in ageing mice. PTH treatment could ameliorate the degenerative changes and improve bone microarchitecture in the subchondral bone by activating bone remodelling. Moreover, PTH inhibited phosphorylation level of Smad3, which can combine with p16(ink4a) gene promoter region, resulting in reduced senescent cells accumulation and increased cellular proliferation of marrow mesenchymal stem cells (MSCs). ELISA also showed relieved levels of specific senescent-associated secretory phenotype (SASP) in ageing mice after PTH treatment.Conclusions In summary, PTH may reduce the accumulation of senescent cells in subchondral bone by inhibiting p16(ink4a) and improve bone marrow microenvironment to active bone remodelling process, indicating PTH administration could be a potential preventative and therapeutic treatment for age-related TMJ OA.