Department of Orthopaedic Surgery, Experimental Orthopaedics, Center for Medical Biotechnology, University of Regensburg, Regensburg, Germany.
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany.
Front Immunol. 2021 Aug 27;12:722884. doi: 10.3389/fimmu.2021.722884. eCollection 2021.
Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.
骨关节炎（OA）是一种退行性关节疾病，不仅会导致软骨丧失，还会导致所有关节组织的结构损伤。关节由α降钙素基因相关肽（αCGRP）和 P 物质（SP）阳性感觉神经纤维支配。感觉关节神经支配的改变可能部分导致关节退行性变化，从而导致 OA 的发展。因此，我们的目的是分析和比较 SP 和 αCGRP 对 OA 患者和非 OA 软骨供体关节软骨细胞代谢的分子影响。我们用 SP 或 αCGRP 处理细胞，并分析这些神经肽对软骨细胞代谢和信号通路调节的影响。在健康软骨的软骨细胞中，与 OA 软骨细胞相比，SP 的作用很小，SP 诱导了炎症介质，抑制了软骨生成标志物，并促进了细胞凋亡和衰老。αCGRP 的处理也增加了 OA 软骨细胞的细胞凋亡和衰老，并减少了软骨生成标志物的表达，但在健康软骨细胞中刺激了合成代谢和保护反应。SP 和 αCGRP 的分解代谢影响可能是由于 ERK 信号的激活所致，而增加的 cAMP 反应可以抵消这种激活。我们认为，在结合其配体 SP 或 αCGRP 后，相应受体的 G 亚基之间的转换在介导感觉神经肽对软骨细胞的观察到的作用中起核心作用。
