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Int J Oral Sci. 2018 Jun 12;10(2):20. doi: 10.1038/s41368-018-0021-2.

Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity.

Author information

1
Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland. mariya.asparuhova@zmk.unibe.ch.
2
Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Bern, Switzerland.
3
Department of Oral Surgery and Stomatology, School of Dental Medicine, University of Bern, Bern, Switzerland.
4
Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Universitat Internacional de Catalunya, Barcelona, Spain.

Abstract

Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral (DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P < 0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2 was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.

PMID:
29895828
PMCID:
PMC5997631
DOI:
10.1038/s41368-018-0021-2
[Indexed for MEDLINE]
Free PMC Article

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