Kurowska Weronika, Slowinska Iwona, Krogulec Zbigniew, Syrowka Piotr, Maslinski Wlodzimierz
Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, 02-637 Warsaw, Poland.
Department of Rheumoorthopaedic Surgery, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, 02-637 Warsaw, Poland.
J Clin Med. 2021 Apr 19;10(8):1778. doi: 10.3390/jcm10081778.
Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators-the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker-C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA.
使骨代谢正常化是类风湿性关节炎（RA）治疗中的一项挑战。对小鼠的研究表明，抗瓜氨酸化蛋白抗体（ACPAs）可触发骨髓中破骨细胞的活化和骨吸收。然而，关于ACPAs在人骨髓中的存在情况及其作用的数据却很稀少。我们研究了ACPAs是否会促使RA骨髓中的破骨细胞活化和骨侵蚀。使用酶联免疫吸附测定法（ELISAs）检测了RA患者骨髓和外周血中的抗环瓜氨酸肽抗体（抗CCP抗体）、破骨细胞活化指标——抗酒石酸酸性磷酸酶5b（TRAP5b）和组织蛋白酶K，以及骨降解标志物——I型胶原C端肽（CTX-I）。我们发现，RA骨髓中存在的ACPAs与该部位TRAP5b、组织蛋白酶K和CTX-I含量的增加有关。在含有抗CCP抗体的骨髓中，抗瓜氨酸化蛋白抗体（ACPA）诱导骨吸收的关键介质白细胞介素8（IL-8）水平也升高，且与TRAP5b和组织蛋白酶K浓度呈正相关。与外周血相比，骨髓中TRAP5b、组织蛋白酶K、CTX-I和IL-8水平更高，表明这些分子在局部生成。我们的结果补充了动物研究的数据，并突出了ACPAs和骨髓在RA骨吸收中的相关性。
