ASARM‐truncated MEPE and AC‐100 enhance osteogenesis by promoting osteoprogenitor adhesion

Abstract

Matrix extracellular phosphoglycoprotein (MEPE) is a member of the SIBLING (Small Integrin-Binding Ligand, N-linked Glycoprotein) family of secreted glycophosphoproteins. Several previous studies have demonstrated that MEPE and its peptide motif, AC-100, may regulate bone mass and influence osteoblast activity, suggesting its potential for inclusion in novel therapeutic strategies aimed at increasing osteogenesis. Our study uses in vitro approaches to assess how adhesion of nonadherent cells is influenced by MEPE and whether response to MEPE is dependent on the maturity of osteoblastic cells. Truncated MEPE (ASARM removed) or AC-100 enhanced the adhesion, spreading, and focal complex formation of unadhered osteoblastic cells leading to increased differentiation and bone formation after 28 days of culture. Furthermore, addition of truncated MEPE or AC-100 to mature osteoblasts had no significant effect on bone formation. Our data supports an action for truncated MEPE and AC-100 in altering the physiology of immature poorly adherent cells which subsequently influences the way in which these cells interact with a substrate to facilitate their survival and/or commitment to the osteoblast lineage.

The Effect of Matrix Extracellular Phosphoglycoprotein and Its Downstream Osteogenesis-related Gene Expression on the Proliferation and Differentiation of Human Dental Pulp Cells

“…It is reported that the C-terminal product ASARM peptide was able to inhibit mineralization processes in vitro and promote cell adhesion through the arginine-glycine-aspartate (RGD) sequence (8). MEPE with the ASARM peptide deleted promoted bone formation in culture and in mice (19), whereas N-terminal cleavage product from MEPE with RGD motif accelerated mineralization (8). Like other SIBLING proteins such as OPN, DMP-1, and DSP, post-translational modification of MEPE is believed to alter its effects on mineralization.…”

MEPE’s Diverse Effects on Mineralization

“…It is interesting to note that recently MEPE with the ASARM peptide deleted was found to promote bone formation in culture and in mice [14]; similarly, a midterminal fragment of MEPE has been found to enhance cell binding [15] and pulp repair [16]. Thus, distinct components of MEPE appear to have different effects on mineralized tissue formation and signaling processes.…”

The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling

“…This is not the only evidence for a role for MEPE in the promotion of mineralisation. Recently, it has been shown that a truncated form of MEPE, which has the ASARM peptide removed, can promote bone mineralisation in culture and in mice (Sprowson et al 2008). Furthermore, a mid-terminal fragment of MEPE (termed 'AC100') has been shown to enhance cell binding, through the stimulation of focal adhesion kinase and ERK (Hayashibara et al 2004).…”