title: Functional characteristics of mesenchymal stem cells derived from the adipose tissue of a patient with achondroplasia.
abstract: Mesenchymal stem cells (MSCs) can be isolated from various tissues including bone marrow, adipose tissue, skin dermis, and umbilical Wharton's jelly as well as injured tissues. MSCs possess the capacity for self-renewal and the potential for differentiation into adipogenic, osteogenic, and chondrogenic lineages. However, the characteristics of MSCs in injured tissues, such as achondroplasia (ACH), are not well known. In this study, we isolated MSCs from human subcutaneous adipose (ACH-SAMSCs) tissue and circumjacent human adipose tissue of the cartilage (ACH-CAMSCs) from a patient with ACH. We then analyzed the characterization of ACH-SAMSCs and ACH-CAMSCs, compared with normal human dermis-derived MSCs (hDMSCs). In flow cytometry analysis, the isolated ACH-MSCs expressed low levels of CD73, CD90, and CD105, compared with hDMSCs. Moreover, both ACH- SAMSCs and ACH-CAMSCs had constitutionally overactive fibroblast growth factor receptor 3 (FGFR3) and exhibited significantly reduced osteogenic differentiation, compared to enhanced adipogenic differentiation. The activity of extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) was increased in ACH-MSCs. In addition, the efficacy of osteogenic differentiation was slightly restored in osteogenic differentiation medium with MAPKs inhibitors. These results suggest that they play essential roles in MSC differentiation toward adipogenesis in ACH pathology. In conclusion, the identification of the characteristics of ACH-MSCs and the favoring of adipogenic differentiation via the FGFR3/MAPK axis might help to elucidate the pathogenic mechanisms relevant to other skeletal diseases and could provide targets for therapeutic interventions.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon, 200-701, Republic of Korea.|Institute of Medical Science, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
authors.forename: Jeong-Ran
authors.initials: JR
authors.lastname: Park
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon, 200-701, Republic of Korea.
authors.forename: Hanbyeol
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Kangwon National University Hospital, Baengnyeon-ro 156, Chuncheon, Gangwon, 200-722, Republic of Korea.
authors.forename: Chung-Hyo
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon, 200-701, Republic of Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-Do, 200-701, South Korea.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon, 200-701, Republic of Korea. seran.yang@gmail.com.|Institute of Medical Science, Kangwon National University, Chuncheon, 200-701, Republic of Korea. seran.yang@gmail.com.|Stem Cell Institute, Kangwon National University, Chuncheon, 200-701, Republic of Korea. seran.yang@gmail.com.
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Yang
mesh_terms: D000130:Achondroplasia / Q000235:genetics / Q000473:pathology*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D010012:Osteogenesis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Achondroplasia; Adipogenesis; FGFR3; Mesenchymal stem cell