Therapeutic effects of calcitonin gene-related peptide-modified bone marrow mesenchymal stem cells combined with autogenous bone grafting for treatment of osteonecrosis of the femoral head in rabbits

Abstract

Calcitonin gene-related peptide (CGRP) promotes proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which influence bone regeneration and reconstruction. We previously established CGRP-modified BMSCs that express the CGRP gene and demonstrated that this elevated CGRP expression promotes osteogenic differentiation of BMSCs. The current study investigated the therapeutic effects of CGRP-modified BMSCs combined with autogenous bone grafting for the treatment of osteonecrosis of the femoral head (ONFH) in rabbits. ONFH model rabbits were divided into three groups: CGRP, BMSCs/pLV5-CGRP combined with autogenous bone grafting; NC, BMSCs/pLV5-NC combined with autogenous bone grafting; and Blank, BMSCs combined with autogenous bone grafting. After autogenous bone grafting, mRNA and protein expression levels of osteogenesis-related genes (CGRP, OCN, Runx2, BMP-2, and OPG) were measured in the femoral head, as were ALP, laminin, and collagen type I contents. The fraction of trabecular bone area, percentage of empty osteocyte lacunae, maximum compressive strength, and mean elasticity modulus of the femoral head were also determined. Our results demonstrated that CGRP-modified BMSCs combined with autogenous bone grafting accelerated osteogenic differentiation of BMSCs, improved osteogenesis efficiency, and promoted the repair and reconstruction of bone tissue in the femoral head, which significantly improved the success rate of ONFH treatment.