title: 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.
authors.affiliation: Musculoskeletal Research Group, Institute for Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Sprowson
authors.forename: Andrew W
authors.initials: AW
authors.lastname: McCaskie
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birch
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology*; D010750:Phosphoproteins / Q000494:pharmacology*; D051381:Rats
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C417185:Mepe protein, rat; D010750:Phosphoproteins; D000469:Alkaline Phosphatase