title: Autocrine Action of Thrombospondin-2 Determines the Chondrogenic Differentiation Potential and Suppresses Hypertrophic Maturation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.
abstract: Previous studies have shown that mesenchymal stem cell (MSC)-based therapies have varying efficacies for the treatment of various diseases, including cartilage defects. In this study, we demonstrated that the chondrogenic differentiation potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) obtained from different individual donors varies, and we investigated the molecular basis for this variation. Microarray gene expression analysis identified thrombospondin-2 (TSP2) as a candidate gene underlying the interindividual variation in the chondrogenic differentiation potential of hUCB-MSCs. To assess the association between TSP-2 and the differentiation potential, we evaluated chondrogenic differentiation of hUCB-MSCs treated with TSP2 siRNA. In addition, we studied the effect of supplementing exogenous recombinant TSP-2 on TSP2 siRNA-treated hUCB-MSCs. We found that TSP-2 autocrinally promoted chondrogenic differentiation of hUCB-MSCs via the Notch signaling pathway, which was confirmed in MSCs from other sources such as bone marrow and adipose tissue. Interestingly, we observed that TSP-2 attenuated hypertrophy, which inevitably occurs during chondrogenic differentiation of hUCB-MSCs. Our findings indicated that the variable chondrogenic differentiation potential of MSCs obtained from different donors is influenced by the TSP-2 level in the differentiating cells. Thus, the TSP-2 level can be used as a marker to select MSCs with superior chondrogenic differentiation potential for use in cartilage regeneration therapy.
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Sang Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Jueun
authors.initials: J
authors.lastname: Ha
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Wonil
authors.initials: W
authors.lastname: Oh
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, School of Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Byung-Gyu
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Biology, Teachers College, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Biomedical Research Institute, R&D Center, MEDIPOST Co., Ltd., Gyeonggi-do, Republic of Korea.
authors.forename: Hong Bae
authors.initials: HB
authors.lastname: Jeon
mesh_terms: D019898:Autocrine Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy; D007231:Infant, Newborn; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*; D000099262:Thrombospondin 2
chemical_list: D019699:Thrombospondins; D000099262:Thrombospondin 2
keywords: Chondrogenic differentiation; Hypertrophy; Notch signaling; Thrombospondin-2; Umbilical cord blood-derived mesenchymal stem cell