Hypoxia-inducible factor 3-alpha expression is associated with the stable chondrocyte phenotype
Hypoxia-inducible factor 3-alpha expression is associated with the stable chondrocyte phenotype
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DOI：
10.1002/jor.22930
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发表时间：
2015-11-01
影响因子：
2.8
通讯作者：
Johnstone, Brian
中科院分区：
文献类型：
--
作者：
Markway, Brandon D.;Cho, Holly;Johnstone, Brian
低氧诱导因子HIF-1和HIF-2是软骨细胞表型的重要调节因子，但对软骨中的HIF-3知之甚少。本研究的目的是表征HIF-3（HIF 3A）在软骨细胞分化过程中的表达在体外和天然软骨组织。HIF 3A，COL 10A 1和MMP 13在三维培养的健康和骨关节炎（OA）组织的间充质干细胞（MSC）和关节软骨细胞中以及在人胚胎骨骺和成人关节软骨中定量。在软骨形成细胞和组织中，HIF 3A与肥大标志物COL 10A 1和MMP 13呈负相关。在健康软骨细胞中，HIF 3A被地塞米松诱导，并在再分化过程中增加。相比之下，在表达高水平COL 10A 1和MMP 13的软骨分化MSC中，HIF 3A表达极低。HIF 3A在再分化的OA软骨细胞中也低于健康软骨细胞。在人胚胎骨骺组织中，HIF 3A在肥大区的表达最低。与成人关节软骨和再分化软骨细胞相比，胚胎软骨中也发现了不同的剪接模式。这些体外和体内研究结果表明，HIF 3A水平是软骨细胞肥大状态的指标，一种或多种剪接变体可能是软骨细胞表型的重要调节因子。(c)2015骨科研究学会。由威利期刊公司出版J Orthop Res 33：1561-1570，2015.
The hypoxia-inducible factors HIF-1 and HIF-2 are important regulators of the chondrocyte phenotype but little is known about HIF-3 in cartilage. The objective of this study was to characterize HIF-3 (HIF3A) expression during chondrocyte differentiation in vitro and in native cartilage tissues. HIF3A, COL10A1, and MMP13 were quantified in mesenchymal stem cells (MSCs) and articular chondrocytes from healthy and osteoarthritic (OA) tissue in three-dimensional cultures and in human embryonic epiphyses and adult articular cartilage. HIF3A was found to have an inverse association with hypertrophic markers COL10A1 and MMP13 in chondrogenic cells and tissues. In healthy chondrocytes, HIF3A was induced by dexamethasone and increased during redifferentiation. By comparison, HIF3A expression was extremely low in chondrogenically differentiated MSCs expressing high levels of COL10A1 and MMP13. HIF3A was also lower in redifferentiated OA chondrocytes than in healthy chondrocytes. In human embryonic epiphyseal tissue, HIF3A expression was lowest in the hypertrophic zone. Distinct splice patterns were also found in embryonic cartilage when compared with adult articular cartilage and redifferentiated chondrocytes. These in vitro and in vivo findings suggest that HIF3A levels are indicative of the hypertrophic state of chondrogenic cells and one or more splice variants may be important regulators of the chondrocyte phenotype. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1561-1570, 2015.