Osteomodulin Positively Regulates Osteogenesis Through Interaction with BMP2

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2021 Feb 5

PMID 33542209

Citations 22

Authors

Wenzhen Lin

Xiaohan Zhu

Li Gao

Mengying Mao

Daming Gao

Zhengwei Huang

Affiliations

Soon will be listed here.

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.

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References

Merline R, Schaefer R, Schaefer L . The matricellular functions of small leucine-rich proteoglycans (SLRPs). J Cell Commun Signal. 2009; 3(3-4):323-35. PMC: 2778586. DOI: 10.1007/s12079-009-0066-2. View

Moreth K, Iozzo R, Schaefer L . Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation. Cell Cycle. 2012; 11(11):2084-91. PMC: 3368860. DOI: 10.4161/cc.20316. View

McEwan P, Scott P, Bishop P, Bella J . Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans. J Struct Biol. 2006; 155(2):294-305. DOI: 10.1016/j.jsb.2006.01.016. View

Lowery J, Rosen V . The BMP Pathway and Its Inhibitors in the Skeleton. Physiol Rev. 2018; 98(4):2431-2452. DOI: 10.1152/physrev.00028.2017. View

Bonnans C, Chou J, Werb Z . Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014; 15(12):786-801. PMC: 4316204. DOI: 10.1038/nrm3904. View

Nickel J, Mueller T . Specification of BMP Signaling. Cells. 2019; 8(12). PMC: 6953019. DOI: 10.3390/cells8121579. View

Ninomiya K, Miyamoto T, Imai J, Fujita N, Suzuki T, Iwasaki R . Osteoclastic activity induces osteomodulin expression in osteoblasts. Biochem Biophys Res Commun. 2007; 362(2):460-6. DOI: 10.1016/j.bbrc.2007.07.193. View

Hankenson K, Gagne K, Shaughnessy M . Extracellular signaling molecules to promote fracture healing and bone regeneration. Adv Drug Deliv Rev. 2015; 94:3-12. DOI: 10.1016/j.addr.2015.09.008. View

Nikitovic D, Aggelidakis J, Young M, Iozzo R, Karamanos N, N Tzanakakis G . The biology of small leucine-rich proteoglycans in bone pathophysiology. J Biol Chem. 2012; 287(41):33926-33. PMC: 3464503. DOI: 10.1074/jbc.R112.379602. View

10.

Juchtmans N, Dhollander A, Coudenys J, Audenaert E, Pattyn C, Lambrecht S . Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage. Arthritis Rheumatol. 2014; 67(2):435-41. DOI: 10.1002/art.38930. View

11.

Sanchez C, Mazzucchelli G, Lambert C, Comblain F, DePauw E, Henrotin Y . Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study. PLoS One. 2018; 13(3):e0194591. PMC: 5856400. DOI: 10.1371/journal.pone.0194591. View

12.

Ulsamer A, Ortuno M, Ruiz S, Susperregui A, Osses N, Rosa J . BMP-2 induces Osterix expression through up-regulation of Dlx5 and its phosphorylation by p38. J Biol Chem. 2007; 283(7):3816-26. DOI: 10.1074/jbc.M704724200. View

13.

Couble M, Bleicher F, Farges J, Peyrol S, Lucchini M, Magloire H . Immunodetection of osteoadherin in murine tooth extracellular matrices. Histochem Cell Biol. 2003; 121(1):47-53. DOI: 10.1007/s00418-003-0608-2. View

14.

Grant C, Bailey T, Noble W . FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011; 27(7):1017-8. PMC: 3065696. DOI: 10.1093/bioinformatics/btr064. View

15.

Zou W, Wan J, Li M, Xing J, Chen Q, Zhang Z . Small leucine rich proteoglycans in host immunity and renal diseases. J Cell Commun Signal. 2018; 13(4):463-471. PMC: 6946788. DOI: 10.1007/s12079-018-0489-8. View

16.

Dissanayaka W, Hargreaves K, Jin L, Samaranayake L, Zhang C . The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo. Tissue Eng Part A. 2014; 21(3-4):550-63. PMC: 4334476. DOI: 10.1089/ten.TEA.2014.0154. View

17.

Kawecki F, Clafshenkel W, Fortin M, Auger F, Fradette J . Biomimetic Tissue-Engineered Bone Substitutes for Maxillofacial and Craniofacial Repair: The Potential of Cell Sheet Technologies. Adv Healthc Mater. 2017; 7(6):e1700919. DOI: 10.1002/adhm.201700919. View

18.

Ramstad V, Franzen A, Heinegard D, Wendel M, Reinholt F . Ultrastructural distribution of osteoadherin in rat bone shows a pattern similar to that of bone sialoprotein. Calcif Tissue Int. 2002; 72(1):57-64. DOI: 10.1007/s00223-002-2047-9. View

19.

Visscher D, Farre-Guasch E, Helder M, Gibbs S, Forouzanfar T, van Zuijlen P . Advances in Bioprinting Technologies for Craniofacial Reconstruction. Trends Biotechnol. 2016; 34(9):700-710. DOI: 10.1016/j.tibtech.2016.04.001. View

20.

Matsubara T, Kida K, Yamaguchi A, Hata K, Ichida F, Meguro H . BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem. 2008; 283(43):29119-25. PMC: 2662012. DOI: 10.1074/jbc.M801774200. View