title: Osteoclastogenesis in the nonadherent cell population of human bone marrow is inhibited by rhBMP-2 alone or together with rhVEGF.
abstract: During bone development and repair, angiogenesis, osteogenesis, and bone remodeling are closely associated processes that share some common mediators. In the present study nonadherent human bone marrow mononuclear cells under the induction of sRANKL and M-CSF, differentiated into osteoclasts with TRAP-positive staining, VNR expression, and Ca-P resorptive activity. The effects of various combinations of rhBMP-2 (0, 3, 30, and 300 ng/mL) and rhVEGF (0 and 25 ng/mL) on osteoclastogenesis potentials were examined in this experimental system. The percentages of TRAP-positive multiple nucleated cells represent osteoclast differentiation potential, and the percentages of resorptive areas in the Ca-P coated plates resemble osteoclast resorption capability. The presence of rhBMP-2 at 30 and 300 ng/mL showed inhibitory effects on osteoclast differentiation and their resorptive capability in the human osteoclast culture system. rhVEGF (25 ng/mL) enhanced the resorptive function of osteoclast whenever it was used alone or combined with 3 ng/mL rhBMP-2. However, rhVEGF-induced resorptive function was inhibited by 30 ng/mL and 300 ng/mL rhBMP-2 in a dose-dependent manner. Statistical analysis demonstrated that an interactive effect exists between rhBMP-2 and rhVEGF on human osteoclastogenesis. These findings suggested that an interactive regulation may exist between BMPs and VEGF signaling pathways during osteoclastogenesis; exact mechanisms are yet to be elucidated.
authors.affiliation: Department of Trauma and Orthopaedic Surgery, Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, Musgrave Park Hospital, Belfast, BT9 7JB, UK.
authors.forename: Chao
authors.initials: C
authors.lastname: Wan
authors.forename: Qiling
authors.initials: Q
authors.lastname: He
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D007527:Isoenzymes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase