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Osteogenic potential of rhBMP9 combined with a bovine‐derived natural bone mineral scaffold compared to rhBMP2
Author(s) -
FujiokaKobayashi Masako,
Sawada Kosaku,
Kobayashi Eizaburo,
Schaller Benoit,
Zhang Yufeng,
Miron Richard J.
Publication year - 2017
Publication title -
clinical oral implants research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.407
H-Index - 161
eISSN - 1600-0501
pISSN - 0905-7161
DOI - 10.1111/clr.12804
Subject(s) - bone morphogenetic protein 2 , chemistry , osteocalcin , osteoblast , alkaline phosphatase , stromal cell , bone morphogenetic protein , microbiology and biotechnology , medicine , in vitro , biology , biochemistry , gene , enzyme
Objectives Combination therapies of growth factors and scaffolds for bone tissue engineering are becoming routine for clinical use. BMP 9 has previously been characterized as one of the most osteogenic inducers among the BMP superfamily; however, up until recently, BMP 9 has only been available through adenovirus transfection experiments (gene therapy). While recombinant human (rh) BMP 2 is regarded as the gold standard for bone regeneration with recombinant growth factors, recently the successful development of rh BMP 9 brings intriguing new possibilities for future clinical use. The purpose of this pioneering study was to investigate the effects of rh BMP 9 in comparison with rh BMP 2 on an in vitro cell behavior of bone‐forming osteoblasts when combined with a bone grafting material. Material and methods Undifferentiated mouse ST 2 stromal bone marrow cells were seeded onto bovine‐derived natural bone mineral ( NBM ) particles treated with (i) control, (ii) rh BMP 2 (10 ng/ml), (iii) rh BMP 2 (100 ng/ml), (iv) rh BMP 9 (10 ng/ml) and (v) rh BMP 9 (100 ng/ml). The effects of rh BMP s were compared for cell adhesion at 8 h, cell proliferation at 1, 3 and 5 days and osteoblast differentiation as assessed by real‐time PCR at 3 and 14 days for genes encoding Runx2, collagen1alpha2 ( COL 1a2), alkaline phosphatase ( ALP ) and osteocalcin ( OCN ). Furthermore, ALP staining and alizarin red staining were used to investigate localization of osteoblast differentiation marker and mineralization on NBM . Results Although neither rh BMP 2 nor rh BMP 9 influenced cell attachment to NBM particles, both were able to stimulate cell proliferation at 3 days. Furthermore, all concentrations of rh BMP s were able to significantly induce mRNA levels of Runx2, COL 1a2 and OCN at 3 days. Interestingly, only rh BMP 9 was able to significantly upregulate mRNA levels of ALP up to eightfold, and ALP staining up to 25‐fold, when compared to rh BMP 2. In addition, only rh BMP 9 (100 ng/ml) significantly increased alizarin red staining when compared to control and rh BMP 2 (10 ng/ml) samples. Conclusion These results demonstrate that both rh BMP 2 and rh BMP 9 have osteopromotive properties on osteoblast differentiation. It was found that rh BMP 9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rh BMP 2 by demonstrating higher levels of ALP expression and alizarin red staining. Further animal studies comparing both recombinant proteins are necessary to further characterize the osteoinductive potential of BMP 9.