期刊
BIOMATERIALS
卷 35, 期 37, 页码 9747-9754出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.08.007
关键词
Collagen-binding motif peptide; Osteoporosis; Selective differentiation; Osteogenesis; Adipogenesis
资金
- Technology Innovation Development Project - Small and Medium Business Administration of the Republic of Korea [S2043526]
- Bio & Medical Technology Development Program - Ministry of Science, ICT & Future Planning [NRF-2012M3A9C6049727, NRF-2012M3A9C6049728, NRF-2013R1A1A3007591]
- Ewha Womans University
- Korea Evaluation Institute of Industrial Technology (KEIT) [S2043526] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012M3A9C6049727, 2013R1A1A3007591, 2012M3A9C6049728] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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. (C) 2014 Elsevier Ltd. All rights reserved.
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