Osteoadherin serves roles in the regulation of apoptosis and growth in MC3T3‑E1 osteoblast cells

Abstract

Small leucine-rich proteoglycans (SLRPs) are a class of proteoglycans that are characterized by small protein cores and structures of leucine-rich repeats. SLRPs are expressed in most extracellular matrices and share numerous biological functions that are associated with binding of collagens and cell surface receptors. Osteoadherin (also termed osteomodulin) is encoded by the Omd gene and is a keratan sulfate proteoglycan of the class II subfamily of SLRPs. Osteoadherin is highly expressed in mineralized tissues, including bone and dentin; however, it's precise roles remain unknown. The present study determined the Omd expression levels and investigated the effects of over-and under-expression of osteoadherin in osteoblastic cells. Omd mRNA expression increased with osteoblast differentiation in Mc3T3-E1 cells. In c2c12 cells, Omd mRNA expression was induced by bone morphogenetic protein (BMP)2. Reporter assays similarly demonstrated activation of the Omd gene promoter following co-transfection with Smad1 and Smad4, which are intracellular signaling molecules of the BMP2 signaling pathway. Overexpression of Omd increased the viability and decreased caspase 3/7 activity in Mc3T3-E1 cells. By contrast, following transfection with small interfering RNA for Omd, viable cell numbers were decreased and caspase 3/7 activity was increased. Furthermore, overexpression of Omd reduced the expression of ccN family 2 in these cells. These results demonstrate that Omd expression is regulated during osteoblast differentiation, and that the protein product osteoadherin serves roles in the apoptosis and growth of osteoblast cells.

Proteomics of Patient-derived Breast Tumours Identifies a Pro-migratory Osteomodulin-Cyclin Dependent Kinase 1 Axis which Drives Bone Metastasis

“…This idea is supported by our observation of increased osteoblast calcium deposition in response to the highest tested concentrations of rOMD. OMD is known to reduce apoptosis in osteoblasts (28), thus supporting a role for OMD in promoting new bone formation and cell survival. Indeed, in our patient cohort upregulated OMD expression correlates with upregulation of serine 118 phosphorylation on pro-apoptotic protein BCL2-associated agonist of cell death (BAD).…”

“…4B). As OMD has previously been associated with resistance to apoptosis (28), we also tested whether OMD expression affected anoikis resistance and stemness of breast cancer cells through mammosphere formation and mammosphere self-renewal assays. OMD expression showed no significant effect on mammosphere formation or self-renewal (Supplemental Fig.…”

What happens to the osteoporotic bone mesenchymal stem cells? Evidence from RNA sequencing

“…Hodgkinson found Abi3bp-knockout increased BMSC proliferation but limited their motility and ability of osteogenic and adipogenic differentiation, indicating that Abi3bp played a role in switching BMSCs between proliferative and differentiating states 28 . Omd (osteomodulin, also known as osteoadherin; OSAD; SLRR2C) encodes a keratan sulfate proteoglycan and usually highly expressed in mineralized tissues 29 . The protein binds to BMP2 via its terminal leucine-rich repeats and thus promotes BMP/SMAD signal activation, osteogenesis-associated gene transcription and mineralized nodule formation 30 .…”

Novel roles of Tsukushi in signaling pathways and multiple disease processes

“…In recent years, more and more studies have found that SLRPs were involved in regulating multiple signaling pathways that control cell proliferation, differentiation, immunity, inflammation, metabolism, and so on 6,9,17,22,24,32 . Previous studies have suggested that possible mechanisms of action include: (a) structural proteins of ECM, which can maintain the stability of the matrix by affecting signal transduction pathways; (b) mainly located outside the cell, where they are located in multiple signal cascades upstream, it forms a signal‐regulating network and affects intracellular phosphorylation; and (c) interacts with extracellular receptors (such as tyrosine kinase receptors and toll‐like receptors) to initiate downstream signaling pathways.…”

“…Further research found that decorin and podocan are involved in the development of diabetic nephropathy 10,19 . In addition, some studies have found that SLRPs (decorin, biglycan, lumican, TSK, osteoadherin, osteoglycin, asporin) are shown to be involved in the pathogenesis of tumors by modulating the proliferation, apoptosis, invasion, and migration of the cancer cells 8,20–24 …”