Growth Hormone-Releasing Peptide 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.

Purpose: To explore the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model.

Methods: 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 the tendon-bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests. M1 macrophage polarization at the tendon-bone interface was assessed by immunofluorescence staining.

Results: GHRP-2 was found to reduce the expression of Cd86, Nos2, and tnfa (all P < .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 < .01), and the number of M1 was reduced 4 weeks after surgery (P < .01) at the tendon-bone interface. The in vivo experiments also showed that histologic scores and bone mineral density were increased by GHRP-2 at 8 weeks postsurgery (P < .01), suggesting improved healing of the tendon-bone interface. Furthermore, the GHRP-2 group showed a better biomechanical property at both 4 and 8 weeks postsurgery, including maximal failure load, stiffness, and tension (all P < .01), and better gait parameters at 8 weeks postsurgery, including mean area of the left front foot and mean intensity of the right front foot (all P < .05).

Conclusions: GHRP-2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat RCT model.

Clinical Relevance: The present study might be a transitional study to show the efficacy of GHRP-2 in enhancing bone-tendon healing and reduce retear rate after rotator cuff repair.