Promotion of mandibular distraction osteogenesis by parathyroid hormone via macrophage polarization induced through iNOS downregulation

<h2>Abstract</h2><h3>Objective</h3> To investigate whether Parathyroid hormone (PTH) can promote mandibular distraction osteogenesis by regulating macrophage polarization and the underlying mechanisms of this phenomenon. <h3>Methods</h3> Forty-eight Rabbits were used to establish the mandibular distraction osteogenesis experimental model, randomly divided into 2 groups. Intermittent post-operative injections of 20 μg/kg PTH and normal saline were administered to the experimental and control groups, respectively. Regenerated new bone was examined using HE staining, osteoclast numbers were determined through tartrate-resistant acid phosphatase (TRAP) staining, and macrophage polarization markers arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS) expressions were elucidated using immunohistochemistry (IHC), the mRNA expression of CD206, CD11C, Arg1 and iNOS were detected using qPCR. <h3>Results</h3> The bone trabeculae in the experimental group were thicker, with a more homogeneous structure and more new osteoid than in the control group. In the area of distraction osteogenesis, the osteoclast count in the experimental group was higher than in the control group (<i>P</i> <i><</i> <i>0.05</i>). IHC results indicated differential expressions of Arg1 and iNOS in the experimental group compared to the control group (<i>P</i> <i><</i> <i>0.05</i>). Relative mRNA expressions of CD11c and iNOS were lower in the experimental group than in the control group (<i>P</i> <i><</i> <i>0.05</i>), whereas the expressions of CD206 and Arg1 mRNA were higher in the experimental group compared to the control group (<i>P</i> <i><</i> <i>0.05</i>). <h3>Conclusion</h3> Intermittent PTH injections increased macrophage quantity in the mandible generated by distraction osteogenesis, downregulated iNOS, upregulated Arg1, and promoted macrophage polarization from M1 to M2 phenotype, thereby promoting mandibular distraction osteogenesis.