Stage-dependent changes in trabecular bone turnover and osteogenic capacity of marrow cells during development of type II collagen-induced arthritis in mice
Stage-dependent changes in trabecular bone turnover and osteogenic capacity of marrow cells during development of type II collagen-induced arthritis in mice
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DOI：
10.1016/s8756-3282(02)00725-1
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发表时间：
2002-06-01
期刊：
影响因子：
4.1
通讯作者：
Nakamura, T
中科院分区：
文献类型：
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作者：
Nishida, S;Tsurukami, H;Nakamura, T
类风湿关节炎(RA)是一种以炎症性多发性关节炎为特征的疾病，导致关节破坏和骨量减少。然而，在类风湿关节炎患者中，骨量和转换之间的关系尚不清楚。为了阐明骨转换和骨髓成骨能力在关节炎形成过程中对质量和结构的影响，我们对9周龄的DBA1/J小鼠进行了首次免疫后8周的观察。免疫后4周出现局限性关节炎，6周出现进展性关节炎。关节炎小鼠的尿脱氧吡啶酚水平在4周时显著升高，此后一直维持在这一水平。血清骨钙素水平在2周和6周显著低于对照组，但在4周和8周与对照组无显著差异。关节炎组小鼠胫骨近端的三维骨小梁体积在4周时明显小于对照组，6周时进一步减小。骨小梁三维结构参数，如结构模型指数和骨小梁形态因子，分别在4周和6周时增加。8周时，骨小梁破骨细胞数量增加，骨形成率降低。6周时关节炎小鼠胫骨骨髓细胞总数、贴壁基质细胞数和矿化结节形成面积均显著低于对照组。成纤维细胞总集落形成单位(CFU-f)和碱性磷酸酶(ALP)阳性的CFU-f集落数量也减少。然而，在关节炎组和对照组之间，校正了总的骨髓基质细胞和/或黏附的基质细胞的这些成骨参数的值没有显著差异。这些数据表明，在局限性关节炎阶段，骨吸收的增加导致骨小梁减少和三维结构恶化。晚期关节炎患者骨髓成骨能力下降是由于骨髓细胞总数减少所致，对成骨细胞分化无明显影响。在这种关节炎模型中，骨形成的减少可能不是很明显。(C)2002年，爱思唯尔科学公司。保留所有权利。
Rheumatoid arthritis (RA) is a disease characterized by inflammatory polyarthritis leading to destruction of the joints and reduction in bone mass. However, the relationship between bone mass and turnover is not yet clear in RA patients. To clarify the effect of bone turnover and marrow osteogenic capacity on mass and structure during the development of arthritis, we examined DBA1/J mice for 8 weeks after the first immunization with bovine type 11 collagen at the age of 9 weeks. Localized arthritis developed at 4 weeks and advanced arthritis at 6 weeks postimmunization. Urinary deoxypyridinoline levels in arthritic mice were significantly higher at 4 weeks, and levels were maintained thereafter. Their serum osteocalcin levels were significantly reduced compared with controls at 2 and 6 weeks, but did not differ significantly from those in the control group at 4 and 8 weeks. Three-dimensional (3D) trabecular bone volume of the proximal tibia measured by 3D microcomputed tomography (micro-CT) in the arthritic mice became significantly lower at 4 weeks and decreased further at 6 weeks compared with controls. Parameters of 3D trabecular bone structure, such as structure model index and trabecular bone pattern factor, were increased at 4 and 6 weeks, respectively. Trabecular osteoclast number increased and bone formation rates decreased at 8 weeks. The number of total bone marrow cells (BMCs), adherent stromal cells, and area of mineralized nodule formation in the tibia of arthritic mice were significantly reduced compared with controls at 6 weeks. Numbers of total fibroblastic colony-forming units (CFU-f) and alkaline phosphatase (ALP)-positive CFU-f colonies also decreased. However, the values of these osteogenic parameters corrected for the total BMCs and/or adherent stromal cells did not differ significantly between the arthritic and control groups. These data indicate that an increase in bone resorption led to the reduction in trabecular bone mass and deterioration of 3D structure during the localized arthritic stage. The reduction in bone marrow osteogenic potential in the advanced arthritic stage was due to the reduction in the number of total bone marrow cells, and differentiation of osteogenic cells was apparently unaffected. The reduction in bone formation may not be substantial in this arthritic model. (C) 2002 by Elsevier Science Inc. All rights reserved.