Bone substitute materials supplemented with prolyl hydroxylase inhibitors decrease osteoclastogenesis in vitro.

Vinzenz, Philipp; Schröckmair, Stefan; Gruber, Reinhard; Agis, Hermann (2015). Bone substitute materials supplemented with prolyl hydroxylase inhibitors decrease osteoclastogenesis in vitro. Journal of biomedical materials research. Part B - applied biomaterials, 103(6), pp. 1198-1203. John Wiley & Sons 10.1002/jbm.b.33295

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BACKGROUND AND OBJECTIVE Inhibition of prolyl hydroxylases stimulates bone regeneration. Consequently, bone substitute materials were developed that release prolyl hydroxylase inhibitors. However, the impact of prolyl hydroxylase inhibitors released from these carriers on osteoclastogenesis is not clear. We therefore assessed the effect of bone substitute materials that release prolyl hydroxylase inhibitors on osteoclastogenesis. MATERIAL AND METHODS Dimethyloxalylglycine, desferrioxamine, and l-mimosine were lyophilized onto bovine bone mineral and hydroxyapatite, and supernatants were generated. Osteoclastogenesis was induced in murine bone marrow cultures in the presence of the supernatants from bone substitute materials. The formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP activity were determined. To test for possible effects on osteoclast progenitor cells, we measured the effect of the supernatants on proliferation and viability. In addition, experiments were performed where prolyl hydroxylase inhibitors were directly added to the bone marrow cultures. RESULTS We found that prolyl hydroxylase inhibitors released within the first hours from bone substitute materials reduce the number and activity of TRAP-positive multinucleated cells. In line with this, addition of prolyl hydroxylase inhibitors directly to the bone marrow cultures dose-dependently reduced the number of TRAP-positive multinucleated cells and the overall resorption activity. Moreover, the released prolyl hydroxylase inhibitors decreased proliferation but not viability of osteoclast progenitor cells. CONCLUSION Our results show that prolyl hydroxylase inhibitors released from bone substitute materials decrease osteoclastogenesis in murine bone marrow cultures.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Periodontics Research

UniBE Contributor:

Gruber, Reinhard


600 Technology > 610 Medicine & health




John Wiley & Sons




Eveline Carmen Schuler

Date Deposited:

03 Nov 2015 07:41

Last Modified:

25 Jan 2017 12:15

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

bone, bone graft, bone remodeling, cell differentiation, drug delivery/release




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