BMP2/7 Heterodimer Can Modulate All Cellular Events of theIn VitroRANKL-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.