CD105 promotes chondrogenesis of synovium-derived mesenchymal stem cells through Smad2 signaling.
Mesenchymal stem cells (MSCs) are considered to be suitable for cell-based tissue regeneration. Expressions of different cell surface markers confer distinct differentiation potential to different sub-populations of MSCs. Understanding the effect of cell surface markers on MSC differentiation is essential to their targeted application in different tissues. Although CD105 positive MSCs possess strong chondrogenic capacity, the underlying mechanisms are not clear. In this study, we observed a considerable heterogeneity with respect to CD105 expression among MSCs isolated from synovium. The CD105(+) and CD105(-) synovium-derived MSCs (SMSCs) were sorted to compare their differentiation capacities and relative gene expressions. CD105(+) subpopulation had higher gene expressions of AGG, COL II and Sox9, and showed a stronger affinity for Alcian blue and immunofluorescent staining for aggrecan and collagenase II, as compared to those in CD105(-) cells. However, no significant difference was observed with respect to gene expressions of ALP, Runx2, LPL and PPARγ. CD105(+) SMSCs showed increased levels of Smad2 phosphorylation, while total Smad2 levels were similar between the two groups. There was no difference in activation of Smad1/5. These results were further confirmed by CD105-knockdown in SMSCs. Our findings suggest a stronger chondrogenic potential of CD105(+) SMSCs in comparison to that of CD105(-) SMSCs and that CD105 enhances chondrogenesis of SMSCs by regulating TGF-β/Smad2 signaling pathway, but not Smad1/5. Our study provides a better understanding of CD105 with respect to chondrogenic differentiation.
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Wenshuai
W
Fan
Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jinghuan
J
Li
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Yiming
Y
Wang
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jianfeng
J
Pan
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shuo
S
Li
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Liang
L
Zhu
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: changanguo@hotmail.com.
Changan
C
Guo
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: yan1002@hotmail.com.
Zuoqin
Z
Yan
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D000071063:Endoglin / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology* / Q000502:physiology
C064206:ENG protein, human; D000071063:Endoglin; C497782:SMAD2 protein, human; D051899:Smad2 Protein
CD105; Cartilage repair; Chondrogenesis; Mesenchymal stem cell; Smad signaling