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Introduction Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and often resulting in long-term impairment.The inferior natural healing responses are attributed mainly to insufficient or failed tenogenesis.The focus of this study is to investigate the growth factors that control tenogenesis of one marrow derived mesenchymal stem cells(BMSCs)in order to optimize tissue engineering techniques for treating tendon disorders.·Subjects and Methods We chose three representative factors from current reported tenogenic factors.We compared the tenogenic efficiency of these three factors(CTGF,GDF-7 and TGF-(B)1)in parallel and establish an efficient inductive approach to induce tenogenesis of mesenchymal stem cells.· Results Based on comparative studies of TGF-(B)1,BMP12,CTGF and their combinations on tenogenic induction of BMSCs,it was found that TGF-(B)1 alone induced teno-lineage specific gene scleraxis expression and collagen production significantly and efficiently.In addition,TGF-(B)1 combined with CTGF elevated tenomodulin mRNA and protein expression at day 7.Hence,the stepwise tenogenic differentiation approach was established by first using TGF-(B)1 stimulation for 3 days followed by combination with CTGF for another 7 days.In ectopic tendon regeneration model and in-situ rat patellar tendon repair,neo-tendon formed by induced BMSCs had much better structural and mechanical properties than did controls,as evidenced by histological analysis,collagen Ⅰ and tenomodulin immunohistochemical staining data,as well as mechanical tests.· Discussion and Conclusion The study demonstrates that induction of BMSCs using growth factors through stepwise differentiation enhances tendon formation and repair.This effective tenogenic approach will not only enhance the effectiveness of the cell therapy in treating tendon disorders,but also can be served as a platform for underlying molecular mechanism research.