Tissue Eng Regen Med.
2017 Aug;14(4):433-441. 10.1007/s13770-017-0046-1.
Recombinant human bone morphogenic protein-2 Induces the Differentiation and Mineralization of Osteoblastic Cells Under Hypoxic Conditions via Activation of Protein Kinase D and p38 Mitogen-Activated Protein Kinase Signaling Pathways
- Affiliations
-
- 1Department of Oral and Maxillofacial Surgery, Pusan National University, Beomeori, Mulgeom, Yangsan 50612, Korea. ydkimdds@pusan.ac.kr
- 2Department of Oral Anatomy, Pusan National University, Yangsan 50612, Korea.
- 3Dental Research Institute, Pusan National University, Yangsan 50612, Korea.
- 4Institute of Translational Dental Sciences, Pusan National University, Yangsan 50612, Korea.
- KMID: 2394977
- DOI: http://doi.org/10.1007/s13770-017-0046-1
Abstract
- Hypoxia suppresses osteoblastic differentiation and the bone-forming capacity. As the leading osteoinductive growth factor used clinically in bone-related regenerative medicine, recombinant human bone morphogenic protein-2 (rhBMP- 2) has yielded promising results in unfavorable hypoxic clinical situations. Although many studies have examined the effects of rhBMP-2 on osteoblastic differentiation, mineralization and the related signaling pathways, those of rhBMP-2 on osteoblastic cells remain unknown, particularly under hypoxic conditions. Therefore, this study was conducted under a 1% oxygen tension to examine the differentiating effects of rhBMP-2 on osteoblastic cells under hypoxia. rhBMP-2 could also induce the differentiation and mineralization of Osteoblastic (MC3T3-E1) cells under1%hypoxic conditions. rhBMP-2 could also induce the differentiation and mineralization of MC3T3-E1 cells under 1% hypoxic conditions. rhBMP-2 increased the alkaline phosphatase {ALP} activity in a time dependent manner, and expression of ALP, collagen type-1 (Col-1) and osteocalcin (OC) mRNAwere up-regulated significantly in a time- and concentration-dependent manner. In addition, the area of the mineralized nodules increased gradually in a concentration-dependent manner. Western blot analysis, which was performed to identify the signaling pathways underlying rhBMP-2-induced osteoblastic differentiation under hypoxic conditions, showed that rhBMP-2 significantly promoted the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) in a time-dependent manner. A pretreatment with SB203580, a p38 MAPK inhibitor, inhibited the rhBMP-2-mediated differentiation and mineralization. Moreover, the phosphorylation of p38 induced by rhBMP-2 was inhibited in response to a pretreatment of the cells with Go6976, a protein kinase D {PKD) inhibitor. These findings suggest that rhBMP-2 induces the differentiation and mineralization of MC3T3-E1 cells under hypoxic conditions via activation of the PKD and p38 MAPK signaling pathways.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Nectandrin A Enhances the BMP-Induced Osteoblastic Differentiation and Mineralization by Activation of p38 MAPK-Smad Signaling Pathway
- IL-1beta Induces Lysozyme Overexpression through a Mechanism Involving ERK/p38 Mitogen Activated Protein Kinase Activation in Human Airway Epithelial Cells
- Ras Mitogen-activated Protein Kinase Signaling and Kinase Suppressor of Ras as Therapeutic Targets for Hepatocellular Carcinoma
- Effect of Mild Hypothermia on the Mitogen Activated Protein Kinases in Experimental Stroke
- Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis
