Bone Abstracts

Introduction: Alcoholism can result in a compromised regenerative capacity of bone and delayed osteointegration of dental implants. One of the mechanisms is that the thereby overdosed all-trans retinoic acid (ATRA), a main metabolite of alcohol, can significantly inhibit osteoblastogenesis. Bone morphogenetic proteins, potent osteinductive growth factors, can be applied to promote osteogenesis. We previously showed that heterodimerized BMP2/7 could promote osteoblastogenesis in a significantly higher dose-efficiency than homodimerized BMP2 or BMP7. In this study, we wish to uncover the antagonism of ATRA to the BMPs of different dimerization types and dose-efficiencies.

Materials and methods: We assessed the antagonism of 1 μM ATRA to either heterodimerized BMP2/7 or homodimerized BMP2 or BMP7 at 50 ng/ml in a well-established eosteoblastogenesis model with pre-osteoblasts (MC3T3-E1). We measured the following parameters: metabolic activity, alkaline phosphatase activity (early differentiation), osteocalcin (late differentiation), mineralization (final differentiation) and the expression of osteoblastogenesis-related genes.

Results: All the three BMPs could significantly enhance ALP, osteocalcin expression and osteoblastogenesis-related genes and BMP2/7 exhibited a significantly higher efficiency than BMP2 or BMP7. ATRA could significantly antagonize such effects of both heterodimerized BMP2/7 and homodimerized BMP2 or BMP7. On the 28th day, BMP2/7, BMP2 and BMP7 resulted in 3-, 1.79- and 1.24-fold mineralization respectively compared with the control (no BMP, no ATRA). However, the addition of ATRA led to a significantly decreased mineralization to a similar level as the control irrespective of BMPs’ dimerization types and potencies.

Conclusions: The advantageous osteoinductivity of heterodimerized BMP2/7 over the homodimerized ones was significantly compromised by ATRA.