title: Determination of osteogenic or adipogenic lineages in muscle-derived stem cells (MDSCs) by a collagen-binding peptide (CBP) derived from bone sialoprotein (BSP).
abstract: Bone sialoprotein (BSP) is a mineralized, tissue-specific, non-collagenous protein that is normally expressed only in mineralized tissues such as bone, dentin, cementum, and calcified cartilage, and at sites of new mineral formation. The binding of BSP to collagen is thought to be important for initiating bone mineralization and bone cell adhesion to the mineralized matrix. Several recent studies have isolated stem cells from muscle tissue, but their functional properties are still unclear. In this study, we examined the effects of a synthetic collagen-binding peptide (CBP) on the differentiation efficiency of muscle-derived stem cells (MDSCs). The CBP sequence (NGVFKYRPRYYLYKHAYFYPHLKRFPVQ) corresponds to residues 35-62 of bone sialoprotein (BSP), which are located within the collagen-binding domain in BSP. Interestingly, this synthetic CBP inhibited adipogenic differentiation but increased osteogenic differentiation in MDSCs. The CBP also induced expression of osteoblastic marker proteins, including alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx2), and osteocalcin; prevented adipogenic differentiation in MDSCs; and down-regulated adipose-specific mRNAs, such as adipocyte protein 2 (aP2) and peroxisome proliferator-activated receptor γ. The CBP increased Extracellular signal-regulated kinases (ERK) 1/2 protein phosphorylation, which is important in lineage determination. These observations suggest that this CBP determines the osteogenic or adipogenic lineage in MDSCs by activating ERK1/2. Taken together, a novel CBP could be a useful candidate for regenerating bone and treating osteoporosis, which result from an imbalance in osteogenesis and adipogenesis differentiation.
authors.affiliation: Dental Regenerative Biotechnology Major, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jue Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000595:Amino Acid Sequence; D019070:Cell Lineage; D002469:Cell Separation; D003094:Collagen / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000737:chemistry / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D012795:Sialoglycoproteins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D003470:Culture Media; D058574:Integrin-Binding Sialoprotein; D010446:Peptide Fragments; D010455:Peptides; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; D003094:Collagen; D020929:Mitogen-Activated Protein Kinase Kinases