Interaction between zonal populations of articular chondrocytes suppresses chondrocyte mineralization and this process is mediated by PTHrP
Interaction between zonal populations of articular chondrocytes suppresses chondrocyte mineralization and this process is mediated by PTHrP
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DOI：
10.1016/j.joca.2007.05.014
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发表时间：
2008-01-01
影响因子：
7
通讯作者：
Lu, H. H.
中科院分区：
文献类型：
--
作者：
Jiang, J.;Leong, N. L.;Lu, H. H.
目的：关节软骨与软骨下骨之间由潮标和软骨钙化带分隔。钙化区域的推进和潮标重复是骨关节炎（OA）的标志。目前，控制出生后关节软骨矿化的机制知之甚少。本研究的目的是测试的假设，不同的软骨层之间的细胞通讯调节关节软骨细胞mineralization.Design：共培养模型建立，以评估来自关节软骨的表面，中间和深区的软骨细胞的相互作用。用三碘甲腺原氨酸（T3）刺激培养物以促进软骨细胞肥大。结果：与表层软骨细胞（SZCs）共培养的深层软骨细胞（DZCs）抑制了T3诱导的碱性磷酸酶（ALP）活性和相关矿化的增加。此外，与对照组相比，SZC-DZC共培养与显着更高的甲状旁腺激素相关肽（PTHrP）表达相关。当将PTHrP（1-40）添加到仅DZC培养物中时，其抑制DZC ALP活性，类似于在与SZC共培养物中观察到的抑制。此外，PTHrP治疗逆转了T3刺激对DZC培养物中肥大标志物（印度刺猬，ALP，基质金属蛋白酶-13，X型胶原）表达的影响。此外，阻断PTHrP的作用显着增加ALP活性在SZC + DZC co-culture.Conclusion：我们的研究结果表明，带状软骨细胞的相互作用在调节细胞矿化的作用，并提供了一个合理的机制，为出生后的调节关节软骨基质组织。这些发现对理解关节软骨的病理学以及制定功能性软骨修复策略也有重要意义。(c)2007年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Articular cartilage is separated from subchondral bone by the tidemark and a calcified cartilage zone. Advancement of the calcified region and tidemark duplication are both hallmarks of osteoarthritis (OA). Currently the mechanisms controlling post-natal articular cartilage mineralization are poorly understood. The objective of this study is to test the hypothesis that cellular communication between different cartilage layers regulates articular chondrocyte mineralization.Design: Co-culture models were established to evaluate the interaction of chondrocytes derived from the surface, middle and deep zones of articular cartilage. The cultures were stimulated with triiodothyronine (T3) to promote chondrocyte hypertrophy. The effects of zonal chondrocyte interactions on chondrocyte mineralization were examined over time.Results: Co-culture of deep zone chondrocytes (DZCs) with surface zone chondrocytes (SZCs) suppressed the T3-induced increase in alkaline phosphatase (ALP) activity and related mineralization. Moreover, SZC-DZC co-culture was associated with a significantly higher parathyroid hormone-related peptide (PTHrP) expression when compared to controls. When PTHrP(1-40) was added to the DZC-only culture, it suppressed DZC ALP activity similar to the inhibition observed in co-culture with SZC. In addition, treatment with PTHrP reversed the effect of T3 stimulation on the expression of hypertrophic markers (Indian hedgehog, ALP, matrix metalloproteinases-13, Type X collagen) in the DZC cultures. Moreover, blocking the action of PTHrP significantly increased ALP activity in SZC + DZC co-culture.Conclusion: Our findings demonstrate the role of zonal chondrocyte interactions in regulating cell mineralization and provide a plausible mechanism for the post-natal regulation of articular cartilage matrix organization. These findings also have significant implications in understanding the pathology of articular cartilage as well as devising strategies for functional cartilage repair. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.