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Specific MicroRNAs Found in Extracellular Matrix Vesicles Regulate Proliferation and Differentiation in Growth Plate Chondrocytes
Calcified Tissue International ( IF 3.3 ) Pub Date : 2021-05-05 , DOI: 10.1007/s00223-021-00855-y
Niels C Asmussen 1 , David J Cohen 2 , Zhao Lin 3 , Michael J McClure 2 , Barbara D Boyan 2, 4 , Zvi Schwartz 2, 5
Affiliation  

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.



中文翻译:

在细胞外基质囊泡中发现的特定 microRNA 调节生长板软骨细胞的增殖和分化

基质囊泡 (MV) 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。MV 的大小与外泌体相似,但它们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基质加工酶和特定于其成熟区域的 microRNA。肋软骨静止区(RC)软骨细胞产生的MV富含microRNA 503,而生长区(GC)软骨细胞产生的MV富含microRNA 122。MV由软骨细胞在激素和因子调节下包装,并将其内容物释放到ECM中也受激素控制,这表明它们的 microRNA 可能在生长板增殖和成熟中具有调节作用。为了测试这个,我们选择了这些富集的 microRNA 的一个子集,并将合成模拟物转回 RC 和 GC 细胞。用选择的 microRNA 转染生长板软骨细胞产生了广泛的表型反应,表明基于 MV 的 microRNA 参与了这些细胞的调节。具体来说,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 控制调节因子的产生。该研究证明了生长板软骨细胞上独特的 MV 富集 microRNA 所具有的强大调节能力及其作为治疗剂的潜力。用选择的 microRNA 转染生长板软骨细胞产生了广泛的表型反应,表明基于 MV 的 microRNA 参与了这些细胞的调节。具体来说,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 控制调节因子的产生。该研究证明了生长板软骨细胞上独特的 MV 富集 microRNA 所具有的强大调节能力及其作为治疗剂的潜力。用选择的 microRNA 转染生长板软骨细胞产生了广泛的表型反应,表明基于 MV 的 microRNA 参与了这些细胞的调节。具体来说,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 控制调节因子的产生。该研究证明了生长板软骨细胞上独特的 MV 富集 microRNA 所具有的强大调节能力及其作为治疗剂的潜力。稳定基质并抑制分化,而 microRNA 22 控制调节因子的产生。该研究证明了生长板软骨细胞上独特的 MV 富集 microRNA 所具有的强大调节能力及其作为治疗剂的潜力。稳定基质并抑制分化,而 microRNA 22 控制调节因子的产生。该研究证明了生长板软骨细胞上独特的 MV 富集 microRNA 所具有的强大调节能力及其作为治疗剂的潜力。

更新日期:2021-05-05
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