Recombinant human bone morphogenetic protein (rhBMP)9 induces osteoblast differentiation when combined with demineralized freeze-dried bone allografts (DFDBAs) or biphasic calcium phosphate (BCP)

Kobayashi, Masako; Schaller, Benoît; Zhang, Yufeng; Kandalam, Umadevi; Hernandez, Maria; Miron, Richard John (2017). Recombinant human bone morphogenetic protein (rhBMP)9 induces osteoblast differentiation when combined with demineralized freeze-dried bone allografts (DFDBAs) or biphasic calcium phosphate (BCP). Clinical oral investigations, 21(5), pp. 1883-1893. Springer 10.1007/s00784-016-1983-0

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OBJECTIVES: Recently, recombinant human bone morphogenetic protein 9 (rhBMP9) has been characterized as one of the most osteogenic growth factors among the 15 human BMPs. The aim of the present study was to investigate the effects of rhBMP9 in comparison to the clinically utilized rhBMP2 on in vitro cell behavior when combined with two bone graft materials including demineralized freeze-dried bone allografts (DFDBAs) and biphasic calcium phosphate (BCP). MATERIALS AND METHODS: The absorption and release kinetics of rhBMPs from DFDBA and BCP were investigated by ELISA. Moreover, murine bone stromal ST2 cell behavior was investigated on DFDBA or BCP seeded on (1) graft only, (2) rhBMP2 (10 ng/ml), (3) rhBMP2 (100 ng/ml), (4) rhBMP9 (10 ng/ml), and (5) rhBMP9 (100 ng/ml). The effects of rhBMPs on DFDBA and BCP were assessed for cell adhesion, proliferation, and osteoblast differentiation by alkaline phosphatase (ALP) activity, alizarin red staining, and real-time PCR for genes encoding Runx2, ALP, and bone sialoprotein (BSP). RESULTS: While both BMPs were gradually released from DFDBA and BCP over time, significantly higher adsorption was observed on BCP when compared to DFDBA. Cell attachment and proliferation was higher on BCP with little influence of either rhBMP2/9. Despite rhBMPs having relatively no effect on cell attachment/proliferation, a pronounced and marked effect was observed on osteoblast differentiation for both rhBMP2/9. Interestingly, it was observed that rhBMP9 induced significantly higher ALP activity, alizarin red staining, and messenger RNA (mRNA) levels of ALP and BSP when compared to rhBMP2. Our results also revealed higher differentiation for rhBMP2/9 with BCP when compared to DFDBA most likely as a result of higher growth factor adsorption. CONCLUSION: While both rhBMP2/9 combined with DFDBA or BCP induced osteoblast differentiation, rhBMP9 induced greater osteoblast differentiation when compared to rhBMP2. CLINICAL RELEVANCE: rhBMP9 may be a recombinant growth factor with higher potential to induce new bone formation when compared to rhBMP2. Further in vivo studies are necessary to characterize its regenerative potential in various animal models. KEYWORDS: BCP; BMP2; BMP9; Biphasic calcium phosphate; Bone morphogenetic proteins; Bone regeneration; Bone tissue engineering; DFDBA; Demineralized freeze-dried bone allografts

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Schädel-, Kiefer- und Gesichtschirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Schädel-, Kiefer- und Gesichtschirurgie

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Craniomaxillofacial Surgery

UniBE Contributor:

Kobayashi, Masako; Schaller, Benoît and Miron, Richard John

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-6981

Publisher:

Springer

Language:

English

Submitter:

Caroline Dominique Zürcher

Date Deposited:

17 May 2017 14:21

Last Modified:

26 May 2017 01:31

Publisher DOI:

10.1007/s00784-016-1983-0

PubMed ID:

27771827

Uncontrolled Keywords:

BCP; BMP2; BMP9; Biphasic calcium phosphate; Bone morphogenetic proteins; Bone regeneration; Bone tissue engineering; DFDBA; Demineralized freeze-dried bone allografts

BORIS DOI:

10.7892/boris.95120

URI:

https://boris.unibe.ch/id/eprint/95120

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