Miacalcic Enhances Rotator Cuff Injury Healing in Osteoporotic Mice by Stimulating Neovascularization via the JAK Pathway

Objective: Rotator cuff tears (RCT) are prevalent among the elderly and often lead to significant shoulder pain. While both open and arthroscopic cuff repairs are effective, the recurrence of RCT post-surgery remains high, with osteoporosis being a major contributing risk factor. Local angiogenesis and tendon-bone healing are essential for optimal recovery after rotator cuff repair. This study investigates the effects of Miacalcic, an osteoporosis medication, on rotator cuff repair in osteoporotic conditions.

Methods: To explore the mechanisms underlying Miacalcic's action, we conducted RNA-sequencing and cell-based experiments on bone marrow-derived mesenchymal stem cells (BMSC) and human umbilical vein endothelial cells (HUVECs). Additionally, an osteoporotic mouse model of RCT was utilized to assess in vivo effects.

Results: Our findings revealed that Miacalcic had no significant effect on the proliferation of BMSCs, whereas it notably stimulated the proliferation of HUVECs. Miacalcic also significantly reduced Apoptosis in HUVECs and enhanced their angiogenic potential. RNA-Seq analysis indicated that Miacalcic primarily modulates the JAK signaling pathway, which plays a key role in angiogenesis. In vivo, Miacalcic treatment in an osteoporotic mouse model enhanced vascularization and facilitated tendon-bone healing in the rotator cuff, leading to improved functional recovery following RCT.

Conclusion: This study highlights the potential of Miacalcic as a therapeutic agent for promoting tendon-bone healing in osteoporotic patients with rotator cuff injuries. By elucidating the mechanisms through which Miacalcic enhances angiogenesis and healing, our findings offer insights into potential strategies for improving post-operative outcomes and reducing RCT recurrence. Further research is necessary to refine our understanding of the specific biological pathways involved and to explore the long-term therapeutic benefits of Miacalcic.