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Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment
Hu, JJ; Yin, Z; Shen, WL; Xie, YB; Zhu, T; Lu, P; Cai, YZ; Kong, MJ; Heng, BC; Zhou, YT; Chen, WS; Chen, X; Ouyang, HW
2016
Source PublicationSTEM CELLS
ISSN1066-5099
Volume34Issue:4Pages:1083-1096
AbstractCalcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment. Stem Cells2016;34:1083-1096
KeywordHypoxia-inducible Factors Vascular Calcification Arterial Calcification Extracellular-matrix Tendon Regeneration Cardiac-glycosides Human Tendinopathy Scleraxis Cartilage Inflammation
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Indexed ByWOS:000374697700023
Language英语
Document Type期刊论文
Identifierhttp://ir.xtbg.org.cn/handle/353005/10219
Collection文献共享
Recommended Citation
GB/T 7714
Hu, JJ,Yin, Z,Shen, WL,et al. Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment[J]. STEM CELLS,2016,34(4):1083-1096.
APA Hu, JJ.,Yin, Z.,Shen, WL.,Xie, YB.,Zhu, T.,...&Ouyang, HW.(2016).Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.STEM CELLS,34(4),1083-1096.
MLA Hu, JJ,et al."Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment".STEM CELLS 34.4(2016):1083-1096.
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