title: BMP2/7 heterodimer can modulate all cellular events of the in vitro RANKL-mediated osteoclastogenesis, respectively, in different dose patterns.
abstract: Bone morphogenetic protein (BMP) heterodimers can trigger and sustain osteoblastic bone regeneration in significantly lower dosages than BMP homodimers. However, their effects on osteoclastic activity-a paramount coupling process with ostoblastic activity-remain undocumented. In this study, we delineated the functional characteristics of BMP2/7 heterodimer in inducing the in vitro osteoclastogenesis. We compared the dose-dependent effects of BMP2/7 heterodimer on the osteoclastogenesis of a preosteoclast cell line (RAW264.7) with those of BMP2 and BMP7 homodimers under the stimulation of 50 ng/mL receptor activator of nuclear factor-κB ligand. We quantitatively monitored the following parameters: cell proliferation, osteoclastic genes expression, morphological characteristics of osteoclasts, and calcium phosphate (CaP) resorption. BMP2/7 heterodimer could dose dependently modulate each osteoclastogenic event with different concentration patterns from the BMP homodimers. All BMPs of 10-150 ng/mL could increase the numbers of osteoclasts. Not BMP7 but 50-200 ng/mL BMP2 homodimer and 100-200 ng/mL BMP2/7 heterodimer could significantly enlarge the average surface-area of an osteoclast. BMP2/7 of 5-150 ng/mL could significantly enhance the osteoclastic CaP resorption to a similar level as the two homodimers. BMP2/7 heterodimer affects every osteoclastogenic event in a complicated dose-dependent manner. Low-concentration BMP2/7 heterodimer may favor a rapid and spontaneous remodeling of its induced bone and, thus, bear a promising potential in cytokine-based tissue engineering.
authors: School of Stomatology/Hangzhou Dental Hospital, Zhejiang Chinese Medical University, Binjiang District, Hangzhou, People's Republic of China.
authors: Yuanna
authors: Y
authors: Zheng
authors: Linhong
authors: L
authors: Wang
authors: Xiaodan
authors: X
authors: Zhang
authors: Xin
authors: X
authors: Zhang
authors: Zhiyuan
authors: Z
authors: Gu
authors: Gang
authors: G
authors: Wu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D055503:Protein Multimerization; D053245:RANK Ligand / Q000378:metabolism*; D023822:Tissue Engineering
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C525820:bmp7 protein, mouse