BMP2/7 heterodimer can modulate all cellular events of the in vitro RANKL-mediated osteoclastogenesis, respectively,...

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.