Korovina Marina O, Valeeva Anna R, Akhtyamov Ildar F, Brooks Wesley, Renaudineau Yves, Manukyan Gayane, Arleevskaya Marina I
Central Research Laboratory, Kazan State Medical Academy, Kazan 420012, Russia.
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan 420008, Russia.
Int J Mol Sci. 2025 Sep 8;26(17):8742. doi: 10.3390/ijms26178742.
Rheumatoid arthritis (RA) and osteoarthritis (OA) are frequently occurring multifactorial diseases affecting joints. OA and RA may share not only tissue locations but also some molecular mechanisms. We compared different pathologies: anti-cyclic citrullinated peptide antibody (ACCP)-positive RA-the classical 'antigen-driven' pathology, starting in synovia with no signs of inflammatory process; ACCP-negative RA, starting with synovial inflammation triggered by nonspecific factors, which becomes a chronic process due to inherited innate immune peculiarities; and OA, starting with inadequate chondrocyte functioning and cartilage degradation with inflammation as a driving force. Notable coincidences in RA and OA development were revealed: shared mutations of 29 genes encoding molecules involved in immune-inflammatory processes and in ECM production; unidirectional association of OA and ACCP-negative RA with non-genetic triggers; and overactivation of signaling pathways with the same consequences for RA and OA. Innate and adaptive immune responses were involved in OA development. Similar to that observed in RA, lymphoid nodular aggregates were revealed in 30% of OA synovia. Myeloid, and especially pauci-immune and fibroid synovial pathotypes, are possible in OA. Indistinguishable from that in RA, pannuses were found in OA articular tissues. Thus, these coincidences may be evidence of evolution of some OA variants in RA.
类风湿性关节炎（RA）和骨关节炎（OA）是常见的影响关节的多因素疾病。OA和RA不仅可能有共同的组织部位，还可能有一些共同的分子机制。我们比较了不同的病理情况：抗环瓜氨酸肽抗体（ACCP）阳性的RA——典型的“抗原驱动”病理，始于无炎症过程迹象的滑膜；ACCP阴性的RA，始于由非特异性因素触发的滑膜炎症，由于遗传的先天免疫特性而成为慢性过程；以及OA，始于软骨细胞功能不足和以炎症为驱动力的软骨降解。研究发现RA和OA发展过程中有显著的巧合：29个编码参与免疫炎症过程和细胞外基质（ECM）产生的分子的基因存在共同突变；OA和ACCP阴性的RA与非遗传触发因素存在单向关联；以及信号通路过度激活对RA和OA产生相同的影响。先天免疫和适应性免疫反应参与了OA的发展。与在RA中观察到的情况类似，在30%的OA滑膜中发现了淋巴小结聚集体。OA中可能存在髓样，尤其是寡免疫和纤维样滑膜病理类型。在OA关节组织中发现了与RA中难以区分的血管翳。因此，这些巧合可能是一些OA变体向RA演变的证据。
