Enhancement of jaw bone regeneration via ERK1/2 activation using dedifferentiated fat cells
Autor: | Tsukasa Yanagi, Kae Kakura, Hirofumi Kido, Hiroshi Kajiya, Munehisa Maeshiba, Jun Ohno, Seiichi Fujisaki |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Bone Regeneration Stromal cell MAP Kinase Signaling System Immunology Adipose tissue Bone healing Bone morphogenetic protein 2 03 medical and health sciences 0302 clinical medicine Osteogenesis Adipocytes Animals Immunology and Allergy Medicine Bone regeneration Genetics (clinical) Transplantation business.industry Mesenchymal stem cell Cell Differentiation Osteoblast Cell Biology Rats 030104 developmental biology medicine.anatomical_structure Adipose Tissue Oncology 030220 oncology & carcinogenesis Cancer research Female business |
Zdroj: | Cytotherapy. 23:608-616 |
ISSN: | 1465-3249 |
Popis: | Background aims Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue–derived MSCs (ASCs) and dedifferentiated fat (DFAT) cells. Although ASCs are sometimes transplanted for clinical cytotherapy, the effects of DFAT cell transplantation on mandibular bone healing remain unclear. Methods The authors assessed whether DFAT cells have osteogenerative potential compared with ASCs in rats in vitro. In addition, to elucidate the ability of DFAT cells to regenerate the jaw bone, the authors examined the effects of DFAT cells on new bone formation in a mandibular defect model in (i) 30-week-old rats and (ii) ovariectomy-induced osteoporotic rats in vivo. Results Osteoblast differentiation with bone morphogenetic protein 2 (BMP-2) or osteogenesis-induced medium upregulated the osteogenesis-related molecules in DFAT cells compared with those in ASCs. BMP-2 activated the phosphorylation signaling pathways of ERK1/2 and Smad2 in DFAT cells, but minor Smad1/5/9 activation was noted in ASCs. The transplantation of DFAT cells into normal or ovariectomy-induced osteoporotic rats with mandibular defects promoted new bone formation compared with that seen with ASCs. Conclusions DFAT cells promoted osteoblast differentiation and new bone formation through ERK1/2 and Smad2 signaling pathways in vitro. The transplantation of DFAT cells promoted new mandibular bone formation in vivo compared with that seen with ASCs. These results suggest that transplantation of ERK1/2-activated DFAT cells shorten the mandibular bone healing process in cytotherapy. |
Databáze: | OpenAIRE |
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