Investigation on the role of Icariin in tendon injury repair: focusing on tendon stem cell differentiation

OBJECTIVE: Tendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries. METHODS: In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01-100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery. RESULTS: In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups. CONCLUSION: ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.