PMID- 28560013 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 9 IP - 5 DP - 2017 TI - Stromal cell-derived factor-1alpha and transforming growth factor-beta(1) synergistically facilitate migration and chondrogenesis of synovium-derived stem cells through MAPK pathways. PG - 2656-2667 AB - The clinical translation of tissue engineering methods is confined by the limited external cell sources, which is hopefully to be addressed by the cell guidance approach as cytokine-induced homing and differentiation of the patients' autologous cells. Synovium-derived stem cells (SDSCs) are a potent cell source for cartilage restoration due to its intrinsic proximity and tissue-specific chondrogenic capacity. In this study, stromal cell-derived factor-1alpha (SDF-1alpha) in combination with transforming growth factor beta(1) (TGF-beta(1)) were used to induce SDSCs migration and chondrogenesis in vitro. The migration capacity was evaluated by transwell assay and for chondrogenic evaluation, the expression of Sox9, ACAN and COL2A1 were assessed by quantitative RT-PCR while the expression of sulfated GAG and collagen II were evaluated by Alcian Blue stain and immunohistochemistry respectively. Our data showed that SDF-1alpha/CXC chemokine receptor 4 (CXCR4) was involved in SDSCs migration through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Exogenous TGF-beta(1) enhanced SDF-1alpha-induced SDSCs migration in a concentration and time-dependent manner through CXCR4, evidenced as complete blockage by AMD3100, the CXCR4 antagonist and this effect was mediated by extracellular regulated protein kinases (ERK) activation. Moreover, the addition of SDF-1alpha augmented the TGF-beta(1)-induced SDSCs chondrogenesis, evidenced by the increased pellet sizes and the expressions of COL 2A1, ACAN and Sox9. This effect was related to c-Jun N-terminal kinase (JNK) activation. Collectively, these results suggest that SDF-1alpha and TGF-beta(1) interacts with each other and synergistically enhance the SDSCs migration and chondrogenesis through MAPK pathways. FAU - Wang, Yiming AU - Wang Y AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Chen, Jifei AU - Chen J AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Fan, Wenshuai AU - Fan W AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Zhang, Jing AU - Zhang J AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Hua, Bingxuan AU - Hua B AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Sun, Bolin AU - Sun B AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Zhu, Liang AU - Zhu L AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Niu, Xinhao AU - Niu X AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Yan, Zuoqin AU - Yan Z AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. FAU - Guo, Changan AU - Guo C AD - Department of Orthopedics, Zhongshan Hospital, Fudan UniversityShanghai, China. LA - eng PT - Journal Article DEP - 20170515 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC5446545 OTO - NOTNLM OT - Stromal cell-derived factor-1alpha OT - chondrogenesis OT - migration OT - synovium-derived stem cells OT - transforming growth factor-beta1 COIS- None. EDAT- 2017/06/01 06:00 MHDA- 2017/06/01 06:01 PMCR- 2017/05/15 CRDT- 2017/06/01 06:00 PHST- 2017/03/02 00:00 [received] PHST- 2017/05/01 00:00 [accepted] PHST- 2017/06/01 06:00 [entrez] PHST- 2017/06/01 06:00 [pubmed] PHST- 2017/06/01 06:01 [medline] PHST- 2017/05/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2017 May 15;9(5):2656-2667. eCollection 2017.