With increasing age, the microenvironment in the bone marrow is altered, leading to a decrease in bone marrow mesenchymal stem cell (BMSC) differentiation, which reduces the number of bone cells and weakens osteogenic capacity, resulting in osteoporosis (OP). The clinical manifestations of OP include bone loss, bone microstructural destruction and altered bone quality. Bone morphogenetic protein 2 (BMP2) serves an important role in inducing the osteogenic differentiation of mesenchymal stem cells (MSCs). Regulating the bone marrow matrix microenvironment and promoting osteogenic differentiation of BMSCs is of significance for both the prevention and treatment of OP. In the present study, isobaric tags for relative and absolute quantification (iTRAQ) high-throughput proteomics technology was combined with bioinformatics analysis to screen 249 differentially expressed proteins in human MSCs overexpressing BMP2, of which 173 were upregulated and 76 proteins were downregulated. The proteins were also involved in signaling pathways associated with extracellular matrix organization, osteoblast differentiation, ossification, bone development, chondrocyte differentiation and bone morphogenesis. By carefully screening the proteins, N-cadherin (CDH2), a protein with osteogenic differentiation potential, was verified by perturbations in the background of BMP2 overexpression. The role of CDH3 in the osteogenic differentiation of MSCs was confirmed by the regulation of several cognate osteogenic markers, suggesting CDH2 as a promising candidate in the field of osteogenesis.

The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.