Bone-cartilage crosstalk: a conversation for understanding the pathogenesis and new treatment strategy of osteoarthritis

doi:10.3969/j.issn.2095-4344.2017.24.026

Abstract

Abstract:

BACKGROUND: Osteoarthritis, a degenerative joint disease, is not only a result from the breakdown of joint cartilage and underlying bone, but also an imbalance of bone remodeling and crosstalk among tissues in the joints.
OBJECTIVE: To review the effect of bone-cartilage crosstalk in the progression of osteoarthritis and its new treatment strategy.
METHODS: A computer-based search of PubMed and CNKI databases was performed for relevant literatures about the relationship between the progress of osteoarthritis and the bone-cartilage crosstalk published from 2007 to 2017. The keywords were “cartilage, interaction, osteoarthritis, pathogenesis, cytokines, signaling pathway” in English and Chinese, respectively. The relationship between the progress of osteoarthritis and the bone-cartilage crosstalk was summarized in views of cytokines, signaling pathway, and new treatment strategy.
RESULTS AND CONCLUSION: Totally 169 articles were retrieved, and finally 54 eligible papers were enrolled based on the inclusion and exclusion criteria. There is a close physical association between subchondral bone and cartilage, and the bone-cartilage interface is a functioning synergistic unit. Increased vascularization, micro-crack formation and abnormal bone remodeling may accelerate the molecules transporting from cartilage to bone in osteoarthritis. Therefore, the bone-cartilage crosstalk plays a pivotal role in the occurrence and development of osteoarthritis.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Tissue Engineering, Osteoarthritis, Chemokines, Receptors, Cytokine

CLC Number:

R318

Li Guang-guang, Guo Yang, Dai Guo-da, Ge Wen-jie, Ma Yong, Yuan Han, Dong Wu-xun, Cai Jian-ping. Bone-cartilage crosstalk: a conversation for understanding the pathogenesis and new treatment strategy of osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(24): 3924-3930.

Figures/Tables 2

成骨细胞和破骨细胞分别引起骨基质形成和退化，在非正常机械负荷下，两者之间的平衡被破坏，引起了软骨下骨的重塑[10]。由此可见，骨代谢失衡可能是骨关节炎形成的重要发病机制。在病变早期，破骨细胞数量增多，骨质大量丢失，骨小梁厚度降低，骨重建发生速率增快，软骨下骨板缓慢增厚，最终导致软骨完全骨化[11]。软骨下骨板孔率的增高和厚度的变薄也与软骨损伤密切相关。在骨关节炎病变后期,成骨细胞活跃，促进骨的形成，增加了骨的密度和体积，导致软骨下骨明显变硬[12]。而在病变末期，软骨下骨厚度增加，硬度降低，钙化作用降低[12-13]。软骨下骨病损是骨关节炎发生发展的风向标，也被认为是引起软骨结构恶化的重要风险因素[14]。骨重建激活局部骨组织自我修复功能，以增加相应的机械负荷，这与病变的发展是一致的。骨体积分数的增加、骨密度的降低以及骨小梁厚度的增加，可代偿关节区域机械活动，但也更容易增加该区域的摩擦[13]。骨髓病损的发生与局部软骨大量丢失有关，骨小梁微观结构的变化可以引起骨髓局部纤维化。利用MRI检测骨髓水肿和软骨下骨囊肿是评估骨关节炎病变的有效依据[15]。破骨细胞过度活跃会在软骨下骨中扩展出一条通道，并最终通过骨垢线到达软骨下骨。血管再生和感觉神经的生长是紧密相连的整体过程，在骨关节炎的病变过程中，它与分子间增加的交互作用存在潜在联系。血管侵入的区域所形成的通道是由该区域软骨下骨的骨髓被血管内皮生长因子表达的维管组织取代，同时炎性细胞渗透至骨髓中所致[16]。此外，伴随着血管数量的增加，交感神经以及感觉神经从软骨下骨中延伸到骨-软骨通道中，并入侵正常软骨以提高血管通道内神经生长因子的表达[4]。动物模型实验表明，在骨关节炎病变早期，软骨下骨中血管生成活动更加频繁，并伴有血管侵入骨软骨连接处的现象[17]。同时，运输通道(血管通道或是骨髓腔)的增加破坏了骨软骨面，提高了分子克服细胞外基质形成的屏障在关节间穿透的能力。有研究运用光漂白方法，发现在骨关节炎鼠模型中荧光素钠从钙化的软骨扩散到骨软骨面的速率比正常的关节更快，软骨损伤及血管侵入都能够增加扩散的渠道，提高小分子的交互作用[18]。在骨关节炎的病变过程中，骨转换也促进了软骨和软骨下骨之间的交互作用。骨关节炎鼠模型研究的结果显示，在病变早期，随着软骨下骨小梁、骨髓细胞以及关节软骨的生物化学和生物力学的交互作用，软骨下骨板孔隙逐渐增多。研究表明，骨重建发生速率的增快及受其刺激产生的血管因子是骨关节炎发生发展不可或缺的因素[11, 19]。 2.2 骨-软骨交互的细胞相互作用见表1。大量的体外研究表明，软骨细胞、成骨细胞、破骨细胞及骨细胞之间存在紧密的分子交互用[20]。实验结果显示了在人工环境中这些细胞相互作用的潜在机制，并为后续的体内模型试验提供基础。Gabay等[21]发现来自骨关节炎患者软骨下骨的软骨细胞，其合成代谢的分子产物明显增加且表型发生改变。而且，Leyh等认为骨关节炎患者的软骨细胞分泌的多种细胞因子和生长因子促进软骨蛋白多糖的丢失[22]。"

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