Enhanced tenogenic differentiation and tendon-like tissue formation by CHIP overexpression in tendon-derived stem cells.
The carboxyl terminus of Hsc70-interacting protein (CHIP, also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells. The potential function of CHIP in tendon-derived stem cells (TDSCs) remains largely unknown at present. Here, we investigated the effects of CHIP on tenogenic differentiation of TDSCs via lentivirus-mediated overexpression. Forced expression of CHIP induced morphological changes and significantly enhanced cell proliferation, as well as tendon differentiation in vitro. Upon stimulation with differentiation induction medium, CHIP-overexpressing TDSCs displayed significant inhibition of differentiation into osteogenic and adipogenic lineages. Subsequent implantation of TDSCs overexpressing CHIP with collagen sponges into nude mice induced a marked increase in ectopic tendon formation in vivo, compared with the control group. Our findings collectively suggest that CHIP is an important contributory factor to tenogenic tissue formation.
Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Weifeng
W
Han
Institute of Orthopaedics, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, Beijing 100048, China.
Lei
L
Chen
Department of Orthopaedics, Air Force General Hospital, People's Liberation Army of China, Beijing 100142, China.
Junpeng
J
Liu
Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Ai
A
Guo
D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D015870:Gene Expression; D008297:Male; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010012:Osteogenesis / Q000235:genetics; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013710:Tendons / Q000166:cytology / Q000378:metabolism*; D014183:Transplantation, Heterologous; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases
CHIP; differentiation; stem cells; tendon