title: Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation.
abstract: In our previous study, we reported that heparan sulfate 6-O-sulfotransferase‑2 (HS6ST2) plays an important role in the cartilage of patients with osteoarthritis and Kashin-Beck disease and that it regulates aggrecan (Acan) metabolism and the viability of chondrocytes. However, its role in chondrocyte differentiation remains poorly understood. In the present study, we aimed to investigate the role of HS6ST2 in chondrocyte differentiation in vitro using mouse prechondrocytic cells. We found that the overexpression or silencing of HS6ST2 significantly enhanced or abrogated the effects of fibroblast growth factor (FGF)‑2 on chondrocyte growth, respectively. We found that the overexpression of HS6ST2 significantly induced the expression of Acan as well as the amount of total proteoglycans in the prechondrocytic cells in the presence of FGF‑2, whereas the silencing of HS6ST2 caused the opposite effect. Furthermore, the expresssion of FGF‑2‑induced sex‑determining region Y‑type high mobility group box protein 9 (SOX9), a major transcription factor for chondrocyte proliferation and differentiation, was also enhanced or blocked by HS6ST2 overexpression or HS6ST2 knockdown, respectively. Additionally, Wnt/β‑catenin signaling, which inhibited chondrocyte proliferation and differentiation, was suppressed by HS6ST2. Taken together, these data suggest that HS6ST2 plays an important role in regulating chondrocyte growth and differentiation by modulating FGF‑2 signaling, thus indicating that it may be a potential and valuable molecular target for the treatment of skeletal dysplasias, such as dwarfism.
authors.affiliation: Department of Prevention and Health Care, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xichi
authors.initials: X
authors.lastname: Ju
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital of The Medical College of Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Joint Surgery, Xi'an Honghui Hospital, The Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Weikun
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Prevention and Health Care, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory of Orthopedics, Xi'an Honghui Hospital, The Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016222:Fibroblast Growth Factor 2; D015238:Sulfotransferases; C404189:heparan sulfate 6-O-sulfotransferase