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Abstract
To explore the potential of growth hormone-releasing peptide-2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model. The impact of GHRP-2 on M1 macrophage polarization in vitro was determined using real-time polymerase chain reaction, western blot, and immunofluorescence staining. GHRP-2 was then applied in a rat RCT model, and the healing of tendon-bone interface was systemically evaluated by histological staining, radiological assessments, gait analysis, and biomechanical tests. M1 macrophage polarization at the tendon-bone interface was assessed by immunofluorescence staining. GHRP-2 was found to reduce the expression of Cd86, Nos2, and tnfa (All p < 0.01), suggesting inhibited M1 macrophage polarization in vitro. The in vivo experiments showed that the proportion of M1 macrophages was reduced both 2- and 4- weeks after surgery (p < 0.01), and the number of M1 was reduced 4 weeks after surgery (p < 0.01) at the tendon-bone interface. The in vivo experiments also showed that histological scores and bone mineral density were increased by GHRP-2 at 8 weeks postsurgery (p < 0.01), suggesting improved healing of the tendon-bone interface. Furthermore, the GHRP-2 group showed better biomechanical property at both 4 and 8 weeks postsurgery, including maximal failure load, stiffness, and tension (All p < 0.01), and better gait parameters at 8 weeks postsurgery, including mean area of left front foot and mean intensity of right front foot (All p < 0.05). GHRP-2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model. The present study might be a transitional study to demonstrate the efficacy of GHRP-2 in enhancing bone-tendon healing and reduce retear rate after rotator cuff repair.
Published Version
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