title: Selective osteogenesis by a synthetic mineral inducing peptide for the treatment of osteoporosis.
abstract: Mineralization in mammalian cells is accomplished by concerted regulation of protein-based extracellular matrix (ECM) components, such as non-collagenous proteins and collagen fibrils. In this study, we investigated the ability of a collagen-binding motif (CBM) peptide derived from osteopontin to selectively affect osteogenic or adipogenic differentiation in vitro and in vivo. In particular, increased osteogenic differentiation and decreased adipogenic differentiation were observed in human mesenchymal stem cells (hMSCs). Osteocalcin (OCN) protein expression in MC3T3-E1 cells without osteogenic inducers was then investigated following treatment with the CBM peptide. In ovariectomized (OVX) mice, estrogen deficiency induced osteoporosis and increased fat tissue deposition. However, after the CBM peptide or estradiol was injected into the OVX mice for 2 months, the increased serum OCN concentration and alkaline phosphate (ALP) activity were decreased in the estradiol-treated group (OVX-E) and the high-concentration CBM peptide-treated group (OVX-HP). Significant bone loss was also observed in the ovariectomized mice (OVX-PBS). In particular, the bone volume per total volume (BV/TV) and bone mineral density (BMD) were significantly decreased in the OVX mice; however, both of these markers were restored in the OVX-HP group, which also had significantly well-developed bone structure and bone formation. In contrast to the bone structural change, adipose tissue was increased in the OVX-PBS. However, a significant decrease in total fat and subcutaneous fat was observed in the low-concentration CBM peptide-treated group (OVX-LP) and the estradiol-treated group (OVX-E). Taken together, these results suggest that the CBM peptide could be an effective therapeutic agent for osteoporosis due to its selective stimulation of osteogenic differentiation, rather than adipogenesis.
authors.affiliation: Department of Molecular Medicine, School of Medicine, Global Top 5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Park
authors.affiliation: Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul, Republic of Korea.
authors.forename: Jue-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Suh
authors.affiliation: Department of Molecular Medicine, School of Medicine, Global Top 5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Yoon Mi
authors.initials: YM
authors.lastname: Jin
authors.affiliation: Department of Molecular Medicine, School of Medicine, Global Top 5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Yeonsil
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Molecular Medicine, School of Medicine, Global Top 5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul, Republic of Korea; Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul, Republic of Korea. Electronic address: ccpperio@snu.ac.kr.
authors.forename: Chong Pyoung
authors.initials: CP
authors.lastname: Chung
authors.affiliation: Department of Molecular Medicine, School of Medicine, Global Top 5 Research Program, Ewha Womans University, Seoul, Republic of Korea. Electronic address: inhojo@ewha.ac.kr.
authors.forename: Inho
authors.initials: I
authors.lastname: Jo
mesh_terms: D016475:3T3 Cells; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000737:chemistry*; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D053495:Osteopontin; D003094:Collagen
keywords: Adipogenesis; Collagen-binding motif peptide; Osteogenesis; Osteoporosis; Selective differentiation