Department of Anatomy and Cell Biology, Cancer Research and Translational Medicine Research Unit, Medical Research Center Oulu, Faculty of Medicine, University of Oulu, Aapistie 5, Oulu 90014, Finland.
Rheumatology Unit, Oulu University Hospital, Medical Research Center Oulu, Oulu, Finland.
Mediators Inflamm. 2022 May 31;2022:2606916. doi: 10.1155/2022/2606916. eCollection 2022.
Rheumatoid arthritis (RA) and osteoarthritis (OA) are common joint diseases associated with changes in local, as well as systemic bone structure and osteoclast function. We investigated how the different soluble inflammatory stimuli in these diseases can affect osteoclastogenesis and bone resorption . Human peripheral blood mononuclear cell-derived osteoclasts were cultured on bone slices with serum from treatment-naïve RA patients and healthy controls and with synovial fluid samples acquired from RA and OA patients. The concentrations of 29 different cytokines and related proteins, including RANKL and OPG, were analyzed in the fluids tested.
RA serum and synovial fluid increased both osteoclastogenesis and bone resorption. Osteoclastogenesis and activity increased more in the cultures containing OA than RA synovial fluid. The osteoclasts cultured in different culture media exhibited different phenotypes, especially the cells cultured with OA synovial fluid were generally larger and had more nuclei. A general increase in proinflammatory cytokines in RA synovial fluid and serum was found. Surprisingly, OA synovial fluid showed lower levels of osteoclastogenesis inhibiting cytokines, such as IL-4 and IL-10, than RA synovial fluid, which at least partly explains more pronounced osteoclastogenesis. No significant difference was found in RANKL or OPG levels.
The proinflammatory stimulus in OA and RA drives the monocyte differentiation towards inflammatory osteoclastogenesis and altered osteoclast phenotype.
类风湿关节炎(RA)和骨关节炎(OA)是常见的关节疾病,与局部和全身骨结构以及破骨细胞功能的变化有关。我们研究了这些疾病中不同的可溶性炎症刺激物如何影响破骨细胞生成和骨吸收。用人外周血单核细胞来源的破骨细胞在骨切片上培养,这些骨切片分别用人初治 RA 患者和健康对照者的血清以及 RA 和 OA 患者的滑液样本处理。在检测的液体中分析了 29 种不同细胞因子和相关蛋白(包括 RANKL 和 OPG)的浓度。
RA 血清和滑液均增加了破骨细胞生成和骨吸收。在含有 OA 滑液的培养物中,破骨细胞生成和活性增加更多。在不同培养介质中培养的破骨细胞表现出不同的表型,特别是用 OA 滑液培养的细胞通常更大且具有更多核。在 RA 滑液和血清中发现了促炎细胞因子的普遍增加。令人惊讶的是,与 RA 滑液相比,OA 滑液中抑制破骨细胞生成的细胞因子(如 IL-4 和 IL-10)水平较低,这至少部分解释了更明显的破骨细胞生成。RANKL 或 OPG 水平没有明显差异。
OA 和 RA 中的促炎刺激物驱动单核细胞向炎症性破骨细胞生成和破骨细胞表型改变分化。