School of Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA, 23284, USA.
College of Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA, 23284, USA.
Calcif Tissue Int. 2021 Oct;109(4):455-468. doi: 10.1007/s00223-021-00855-y. Epub 2021 May 5.
Matrix vesicles (MVs) are extracellular organelles produced by growth plate cartilage cells in a zone-specific manner. MVs are similar in size to exosomes, but they are tethered to the extracellular matrix (ECM) via integrins. Originally associated with matrix calcification, studies now show that they contain matrix processing enzymes and microRNA that are specific to their zone of maturation. MVs produced by costochondral cartilage resting zone (RC) chondrocytes are enriched in microRNA 503 whereas those produced by growth zone (GC) chondrocytes are enriched in microRNA 122. MVs are packaged by chondrocytes under hormonal and factor regulation and release of their contents into the ECM is also under hormonal control, suggesting that their microRNA might have a regulatory role in growth plate proliferation and maturation. To test this, we selected a subset of these enriched microRNAs and transfected synthetic mimics back into RC and GC cells. Transfecting growth plate chondrocytes with select microRNA produced a broad range of phenotypic responses indicating that MV-based microRNAs are involved in the regulation of these cells. Specifically, microRNA 122 drives both RC and GC cells toward a proliferative phenotype, stabilizes the matrix and inhibits differentiation whereas microRNA 22 exerts control over regulatory factor production. This study demonstrates the strong regulatory capability possessed by unique MV enriched microRNAs on growth plate chondrocytes and their potential for use as therapeutic agents.
基质小泡（MVs）是生长板软骨细胞以区域特异性方式产生的细胞外细胞器。MVs 的大小与外泌体相似，但通过整合素与细胞外基质（ECM）相连。最初与基质钙化有关，现在的研究表明它们含有特定于其成熟区的基质加工酶和 microRNA。来自骺软骨静止区（RC）软骨细胞的 MV 富含 microRNA 503，而来自生长区（GC）软骨细胞的 MV 富含 microRNA 122。MVs 在激素和因子调节下由软骨细胞包装，并通过激素控制其内容物释放到 ECM 中，这表明其 microRNA 可能在生长板增殖和成熟中具有调节作用。为了验证这一点，我们选择了这些富集的 microRNA 中的一部分，并将合成模拟物转染回 RC 和 GC 细胞。用选定的 microRNA 转染生长板软骨细胞会产生广泛的表型反应，表明基于 MV 的 microRNA 参与了这些细胞的调节。具体而言，microRNA 122 驱动 RC 和 GC 细胞向增殖表型发展，稳定基质并抑制分化，而 microRNA 22 则控制调节因子的产生。这项研究表明，独特的 MV 富集 microRNA 对生长板软骨细胞具有很强的调节能力，并且可能用作治疗剂。
