Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells
Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells
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DOI：
10.1152/ajpcell.00398.2009
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发表时间：
2010-02-01
影响因子：
5.5
通讯作者：
Guicheux, Jerome
中科院分区：
文献类型：
--
作者：
Merceron, Christophe;Vinatier, Claire;Guicheux, Jerome
王建国，张晓东，陈晓华，等.低氧对人脂肪干细胞成骨潜能的影响.Am J Physiol Cell Physiol 298：C355-C364,2010。2009年11月25日首次出版；doi：10.1152/ajpcell.00398.2009。-人类脂肪组织来源的干细胞(HATSC)被认为是软骨工程的修复细胞。丰富的培养液和三维环境可以诱导hATSC向软骨细胞分化。鉴于骨是血管化的，而软骨不是，氧分压已被认为是骨软骨分化的调节因素。我们的工作旨在确定缺氧是否影响hATSC的成骨能力。HATSC在软骨性或成骨性介质中、颗粒或单层培养28天，在5%或20%氧分压下培养。用实时荧光定量聚合酶链式反应(COL2A1、聚集素、Runx2和骨钙素)监测细胞分化情况。分别用Alcian蓝染色和糖胺多聚糖(GAG)免疫组织化学染色及II型胶原免疫组织化学染色评价软骨细胞的分化。通过矿化基质(茜素红)染色和碱性磷酸酶(ALP)活性的测定来评估成骨分化。HATSC在软骨细胞培养液中缺氧时，软骨细胞标志物的表达上调。相反，即使在成骨介质存在的情况下，骨钙素的表达、矿化和碱性磷酸酶活性在低氧条件下也严重减少。我们的数据有力地表明，缺氧有利于hATSC的软骨分化，这是通过软骨形成标志物的表达来证明的，但它可以改变其成骨能力。我们的结果强调了缺氧对hATSC的软骨形成和成骨分化过程的不同调节作用。这些数据可以帮助我们挖掘组织工程和干细胞的潜力，以取代或恢复骨关节组织的功能。
Merceron C, Vinatier C, Portron S, Masson M, Amiaud J, Guigand L, Cherel Y, Weiss P, Guicheux J. Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells. Am J Physiol Cell Physiol 298: C355-C364, 2010. First published November 25, 2009; doi: 10.1152/ajpcell.00398.2009.-Human adipose tissue-derived stem cells (hATSC) have been contemplated as reparative cells for cartilage engineering. Chondrogenic differentiation of hATSC can be induced by an enriched culture medium and a three-dimensional environment. Given that bone is vascularized and cartilage is not, oxygen tension has been suggested as a regulatory factor for osteochondrogenic differentiation. Our work aimed at determining whether hypoxia affects the osteochondrogenic potential of hATSC. hATSC were cultured in chondrogenic or osteogenic medium for 28 days, in pellets or monolayers, and under 5% or 20% oxygen tension. Cell differentiation was monitored by real-time PCR (COL2A1, aggrecan, Runx2, and osteocalcin). The chondrogenic differentiation was further evaluated by Alcian blue and immunohistological staining for glycosaminoglycans (GAGs) and type II collagen, respectively. Osteogenic differentiation was also assessed by the staining of mineralized matrix (Alizarin Red) and measurement of alkaline phosphatase (ALP) activity. The expression of chondrogenic markers was upregulated when hATSC were exposed to hypoxia in chondrogenic medium. Conversely, osteocalcin expression, mineralization, and ALP activity were severely reduced under hypoxic conditions even in the presence of osteogenic medium. Our data strongly suggest that hypoxia favors the chondrogenic differentiation of hATSC as evidenced by the expression of the chondrogenic markers, whereas it could alter their osteogenic potential. Our results highlight the differential regulatory role of hypoxia on the chondrogenic and osteogenic differentiation processes of hATSC. These data could help us exploit the potential of tissue engineering and stem cells to replace or restore the function of osteoarticular tissues.