长期固定后，大鼠膝关节中的软骨会被骨取代。

Bone replaces articular cartilage in the rat knee joint after prolonged immobilization.

机构信息

Elizabeth Bruyère Hospital, Ottawa, Ontario, Canada.

Department of Medicine, University of Ottawa, Ontario, Canada.

出版信息

Bone. 2018 Jan;106:42-51. doi: 10.1016/j.bone.2017.09.018. Epub 2017 Sep 30.

DOI:10.1016/j.bone.2017.09.018

PMID:28974461

Abstract

BACKGROUND

Lost joint range of motion (ROM) is common in chronic osteoarthritis, alters regional weight-bearing across the articular surfaces, and contributes to loss of cartilage and bone alterations. Limited data exist on the regional effects on joints subjected to chronic losses of ROM.

OBJECTIVE

To characterize the regional replacement by bone as part of articular cartilage degeneration after prolonged immobilization.

METHODS

Eleven rat knees were rigidly-immobilized in flexion for 32weeks with contralateral and sham-operated (n=6) knees as controls. Sagittal medial tibial epiphysis histological sections assessed the anterior (non-weight-bearing), middle and posterior (both weight-bearing) regions. We quantified the distribution of collagen I, collagen II, cartilage thickness, glycosaminoglycan (GAG) staining, Mankin scoring, and subchondral bone plate cross-sectional area. Using immunohistochemistry (IHC), we visualized blood vessels, osteoblasts, and mesenchymal stem cells (MSCs).

RESULTS

Immobilized cartilage had increased collagen I content in the anterior tibial region with picrosirius red staining (immobilized=61±20%; contralateral=43±12%, p=0.033; sham=20±10%, p=0.028) and collagen I IHC (immobilized=40±10%; contralateral=11±4%, p=0.003; sham=5±3%, p=0.043). Articular cartilage was thinner anteriorly (18±30μm) in immobilized knees versus contralateral (124±40μm, p<0.001) and sham (125±43μm, p=0.043). GAG staining covered 2±4% of the anterior articular area in immobilized knees versus 28±12% contralaterally (p=0.003) and 26±7% in sham (p=0.043). Mankin scores in immobilized knees were 4.7±1.7 versus 0.2±0.4 and 0±0 for contralateral and sham (p=0.003, p=0.042), respectively. The trabecular bone plate area of anterior and posterior regions showed relative loss of cross-sectional area in immobilized knees compared to controls (immobilized/contralateral area ratios of 0.67 and 0.46 respectively, both p=0.003), while the area in the middle region was preserved. Movat's pentachrome stain and CD31 staining showed chondral vascular ingrowth from subchondral bone. Osteocalcin and CD90 MSC staining were decreased in immobilized knees versus contralateral (p=0.003, p=0.036 respectively).

CONCLUSIONS

Bony replacement characterizes articular cartilage degeneration of knees immobilized for 32weeks in the anterior, non-weight bearing region of the tibia. Replacement of cartilage by bone may have been mediated by chondral vascularization, suggesting irreversible changes. These findings stress the importance of weight-bearing and joint motion to maintain cartilage structure.

摘要

背景

慢性骨关节炎中常见的关节活动度丧失（ROM）会改变关节表面的局部负重，并导致软骨和骨的改变。关于长期 ROM 丧失后关节的局部影响，目前数据有限。

目的

描述在长期固定后，作为关节软骨退化的一部分，骨在关节中的区域性替代。

方法

11 个大鼠膝关节采用刚性固定方式在屈曲位固定 32 周，对侧和假手术（n=6）膝关节作为对照。矢状位胫骨内侧骺板组织学切片评估前（非负重）、中、后（均负重）区域。我们定量评估了胶原 I、胶原 II、软骨厚度、糖胺聚糖（GAG）染色、Mankin 评分和软骨下骨板的横截面积。通过免疫组织化学（IHC），我们观察了血管、成骨细胞和间充质干细胞（MSCs）。

结果

与对侧（固定=61±20%；对侧=43±12%，p=0.033；假手术=20±10%，p=0.028）和胶原 I IHC（固定=40±10%；对侧=11±4%，p=0.003；假手术=5±3%，p=0.043）相比，固定后的胫骨前区软骨中胶原 I 含量增加。固定膝关节的关节软骨较对侧（固定=18±30μm；对侧=124±40μm，p<0.001）和假手术（固定=125±43μm，p=0.043）更薄。固定膝关节的 GAG 染色仅覆盖前关节区域的 2±4%，而对侧为 28±12%（p=0.003），假手术为 26±7%（p=0.043）。固定膝关节的 Mankin 评分为 4.7±1.7，而对侧和假手术的评分为 0.2±0.4 和 0±0（p=0.003，p=0.042）。与对照组相比，固定膝关节的前、后区域的小梁骨板面积显示出相对的横截面积损失（固定/对侧面积比分别为 0.67 和 0.46，均 p=0.003），而中间区域的面积保持不变。Movat 的五重染色和 CD31 染色显示软骨下骨的软骨血管生成。与对侧相比，固定膝关节中的骨钙素和 CD90 MSC 染色减少（p=0.003，p=0.036）。