Effect of recombinant human bone morphogenetic protein-2 on bisphosphonate-treated osteoblasts

Abstract

ObjectivesBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling.Materials and MethodsHuman fetal osteoblast cells (hFOB 1.19) were treated with 100 µM alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.ResultsCell viability was decreased to 82.75%±1.00% by alendronate and then increased to 110.43%±1.35% after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2.ConclusionrhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

Combined effect of recombinant human bone morphogenetic protein-2 and low level laser irradiation on bisphosphonate-treated osteoblasts

“…Recombinant human BMP-2 (rhBMP-2), a bone healing activating factor, exhibits osteogenic effects and has been used widely in dental clinics. Through a previous study, we know that rhBMP-2 and LLLT have stimulating effects on BP-treated osteoblasts15. In this study, we investigated the synergic effect of rhBMP-2 and LLLT on BP-treated osteoblasts.…”

Sub‐clinical dose of bone morphogenetic protein‐2 does not precipitate rampant, sustained inflammatory response in bone wound healing

“…There is a paucity of literature studying the effects of the rhBMP2 on nonmature bone cells. One study using fetal osteoblasts did establish rhBMP‐2 can recover M‐CSF expression after bisphosphonate treatment . As M‐CSF is also important in the monocyte/macrophage lineage, specifically for proliferation and differentiation, it is possible rhBMP‐2 may act directly on macrophages.…”

“…One study using fetal osteoblasts did establish rhBMP-2 can recover M-CSF expression after bisphosphonate treatment. 41 As M-CSF is also important in the monocyte/macrophage lineage, specifically for proliferation and differentiation, it is possible rhBMP-2 may act directly on macrophages. Thus, much more work on the effect of rhBMP-2 on macrophages is necessary to completely rule out this specific cell population as being implicated in the heightened inflammation associated with the clinical rhBMP2 dose.…”

Effect of BMPs and Wnt3a co-expression on the osteogenetic capacity of osteoblasts

“…BMPs are part of the TGF-β superfamily, which includes 43 members. It was previously demonstrated that BMPs could induce mesenchymal cells to irreversibly differentiate into cartilages and bone cells in vivo (5)(6)(7). Additionally, the wingless-type mouse mammary tumor virus integration site family is a class of Wnt gene-encoded secretory glycoproteins.…”