Effect of prolyl hydroxylase inhibitor-loaded collagen barrier membranes on osteoclastogenesis and osteoblastogenesis

Prolyl hydroxylase inhibitors induce a proangiogenic response and are therefore proposed to optimize regenerative approaches in periodontics and oral surgery. Here the effect of the prolyl hydroxylase inhibitors dimethyloxalylglycine and deferoxamine, released from collagen barrier membranes, on osteoclastogenesis and osteoblastogenesis was evaluated. Collagen barrier membranes were loaded with dimethyloxalylglycine and deferoxamine. Release studies were performed and supernatants were taken after 1, 3, 6, 24, and 48 h. The effect of these supernatants on osteoblast- and osteoclast-precursor cells was evaluated. Furthermore, dose response studies for dimethyloxalylglycine and deferoxamine were performed. Osteoclastogenesis was evaluated with RAW 264.7 cells based on the number of multinuclear tartrate-resistant acid phosphatase positive cells. Osteoblastogenesis was evaluated with MC3T3-E1 cells based on alkaline phosphatase. Metabolic activity and cell proliferation were assessed based on MTT and BrdU assays. Vascular endothelial growth factor production was evaluated using an immunoassay. We found that supernatants taken in the first hour from collagen barrier membranes loaded with dimethyloxalylglycine or deferoxamine reduced osteoclastogenesis. Osteoblastogenesis was not reduced significantly. Cell proliferation and metabolic activity of RAW 264.7 and MC3T3-E1 cells were inhibited by supernatants of collagen barrier membranes loaded with deferoxamine but not dimethyloxalylglycine. In RAW 264.7 cell culture, vascular endothelial growth factor production was increased only by supernatants of collagen barrier membranes loaded with dimethyloxalylglycine, but not deferoxamine. In MC3T3-E1 cell culture, supernatants of collagen barrier membranes loaded with dimethyloxalylglycine and deferoxamine both increased vascular endothelial growth factor production. Direct measurements showed that the majority of dimethyloxalylglycine and deferoxamine is released in the first hours. Dose-response studies supported the divergent effects of deferoxamine and dimethyloxalylglycine in RAW 264.7 and MC3T3-E1 cultures. Our findings show diverse effects of dimethyloxalylglycine- and deferoxamine-loaded collagen barrier membranes during osteoclastogenesis and osteoblastogenesis. Preclinical studies will reveal if the increase in vascular endothelial growth factor together with the inhibitory effect on osteoclasts can stimulate oral tissue regeneration.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:31

Enthalten in:

Journal of biomaterials applications - 31(2017), 10 vom: 15. Mai, Seite 1370-1379

Sprache:

Englisch

Beteiligte Personen:

Edelmayer, Michael [VerfasserIn]
Al-Habbal, Diana [VerfasserIn]
Pensch, Manuela [VerfasserIn]
Janjić, Klara [VerfasserIn]
Agis, Hermann [VerfasserIn]

Links:

Volltext

Themen:

9007-34-5
Alkaline Phosphatase
Amino Acids, Dicarboxylic
Collagen
Collagen barrier membranes
Deferoxamine
EC 3.1.3.1
EC 3.1.3.2
Guided bone regeneration
Hypoxia inducible factor-1
Hypoxia mimetic agents
J06Y7MXW4D
Journal Article
Oxalylglycine
Prolyl-Hydroxylase Inhibitors
Research Support, Non-U.S. Gov't
Tartrate-Resistant Acid Phosphatase
Tissue engineering
VVW38EB8YS
Vascular Endothelial Growth Factor A

Anmerkungen:

Date Completed 09.10.2018

Date Revised 22.10.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/0885328217702563

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM270646272