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冲击波通过与腺苷和 A2B 受体结合抑制人骨髓间充质干细胞的软骨分化。

Shockwaves Inhibit Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Association with Adenosine and A2B Receptors.

机构信息

Department of Orthopedic Trauma, The first Hospital of Jilin University, Changchun, 130021, China.

Department of Orthopedics, The Bin Zhou People's Hospital, Bin Zhou, 256600, China.

出版信息

Sci Rep. 2017 Oct 30;7(1):14377. doi: 10.1038/s41598-017-14875-y.

DOI:10.1038/s41598-017-14875-y
PMID:29085053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5662611/
Abstract

Extracorporeal shockwave therapy (ESWT) has emerged as the important choice for the treatment of many orthopedic disorders. Our previous mechanistic studies suggest that ESWT promoted osteogenesis of human mesenchymal stem cells (hMSCs) through mechanisms that involve adenosine 5'-triphosphate (ATP) release. In this study, we investigated the effect of ESWT on chondrogenesis of hMSCs. We demonstrate that ESWT treatment caused a significant release of adenosine from hMSCs; ESWT treatment increased the levels of A2B receptor (A2BR) in hMSCs under 3-D culture conditions. ESWT, exogenous adenosine and specialized A2BR agonist suppressed hMSC chondrogenic differentiation through downregulating the expressions of aggrecan (ACAN), Collagen Type I alpha 2(COL1A2), Collagen Type II alpha 1(COL2A1), Sex-Determining Region YBox 9 (SOX9) and Sex-Determining Region YBox 6 (SOX6). Selective A2BR antagonists induced chondrogenic differentiation of hMSCs. This study indicated that shockwave therapy inhibits hMSC chondrogenic differentiation through or partially through regulation of adenosine release and activation of A2B receptor under 3-D culture conditions.

摘要

体外冲击波疗法（ESWT）已成为治疗许多骨科疾病的重要选择。我们之前的机制研究表明，ESWT 通过涉及三磷酸腺苷（ATP）释放的机制促进人间充质干细胞（hMSC）成骨。在这项研究中，我们研究了 ESWT 对 hMSC 软骨形成的影响。我们证明，ESWT 治疗可导致 hMSC 中大量的腺苷释放；在 3D 培养条件下，ESWT 处理增加了 hMSC 中 A2B 受体（A2BR）的水平。ESWT、外源性腺苷和专门的 A2BR 激动剂通过下调聚集蛋白聚糖（ACAN）、I 型胶原α 2（COL1A2）、II 型胶原α 1（COL2A1）、性别决定区 Y 框 9（SOX9）和性别决定区 Y 框 6（SOX6）的表达，抑制 hMSC 软骨分化。选择性 A2BR 拮抗剂诱导 hMSC 软骨分化。本研究表明，在 3D 培养条件下，冲击波治疗通过或部分通过调节腺苷释放和激活 A2B 受体抑制 hMSC 软骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/23c97696f4df/41598_2017_14875_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/9b51a142c35a/41598_2017_14875_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/9d1cd91c35ed/41598_2017_14875_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/5b1a5c7c6810/41598_2017_14875_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/7a2459c92736/41598_2017_14875_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/69fa96e92049/41598_2017_14875_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/23c97696f4df/41598_2017_14875_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/9b51a142c35a/41598_2017_14875_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/9d1cd91c35ed/41598_2017_14875_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/a5902e04aecd/41598_2017_14875_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/7a2459c92736/41598_2017_14875_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/69fa96e92049/41598_2017_14875_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb71/5662611/23c97696f4df/41598_2017_14875_Fig7_HTML.jpg

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