Osteomodulin positively regulates osteogenesis through interaction with BMP2
Open Access
- 1 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (2), 1-13
- https://doi.org/10.1038/s41419-021-03404-5
Abstract
Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, distributes in mineralized tissues and is positively regulated by bone morphogenetic protein 2 (BMP2). However, the exact function of OMD during mineralization and its association with BMP2 remain poorly understood. Herein, the expression pattern of OMD during osteogenesis was investigated in human dental pulp stem cells. Silencing OMD gene significantly suppressed the alkaline phosphatase activity, mineralized nodule formation and osteogenesis-associated gene transcription. Besides, OMD could enhance BMP2-induced expression of SP7 and RUNX2 with concentration dependence in vitro. Rat mandibular bone defect model revealed that scaffolds injected with the combination of OMD and suboptimal BMP2 exhibited more mature and abundant mineralized bone than that treated with OMD or suboptimal BMP2 alone. Mechanistically, OMD could bind to BMP2 via its terminal leucine-rich repeats and formed complexes with BMP2 and its membrane receptors, thus promoting BMP/SMAD signal transduction. In addition, OMD was a putative target gene of SMAD4, which plays a pivotal role in this pathway. Collectively, these data elucidate that OMD may act as a positive coordinator in osteogenesis through BMP2/SMADs signaling.Keywords
Funding Information
- National Natural Science Foundation of China (81570964, 81570964, 81570964, 81570964, 81570964, 81570964)
This publication has 54 references indexed in Scilit:
- Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammationCell Cycle, 2012
- Modulation of canonical Wnt signaling by the extracellular matrix component biglycanProceedings of the National Academy of Sciences of the United States of America, 2011
- FIMO: scanning for occurrences of a given motifBioinformatics, 2011
- Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycansThe FEBS Journal, 2010
- The matricellular functions of small leucine-rich proteoglycans (SLRPs)Journal of Cell Communication and Signaling, 2009
- Bone morphogenetic protein receptors and signal transductionThe Journal of Biochemistry, 2009
- BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineageProceedings of the National Academy of Sciences of the United States of America, 2009
- BMP2 Regulates Osterix through Msx2 and Runx2 during Osteoblast DifferentiationJournal of Biological Chemistry, 2008
- Differential regulation of osteoadherin (OSAD) by TGF-β1 and BMP-2Biochemical and Biophysical Research Communications, 2006
- Ultrastructural Distribution of Osteoadherin in Rat Bone Shows a Pattern Similar to That of Bone SialoproteinCalcified Tissue International, 2003