title: Dexamethasone inhibits the differentiation of rat tendon stem cells into tenocytes by targeting the scleraxis gene.
abstract: Glucocorticoid-induced tendon rupture is very common in clinical practice, and the overall outcome of surgical suture repair is rather poor. The mechanism remains unclear, and effective treatments are still lacking. In the present study, we investigated the effect of dexamethasone on the differentiation of rat tendon stem cells (TSCs) to tenocytes and the underlying molecular mechanisms and found that dexamethasone inhibits the differentiation of TSCs to tenocytes by analyzing the development of long, spindle-shaped cells and detecting the expression of tenocyte markers type I collagen and tenomodulin (TNMD) at both the mRNA and protein levels. We also discovered that after treatment with dexamethasone, the scleraxis expression level is downregulated in vitro and in human specimen. Chromatin immunoprecipitation (ChIP)-PCR showed that dexamethasone promotes glucocorticoid receptor interacted with the TGGAAGCC sequence located between -734 and -726 base pairs (bp) upstream of the start codon of the scleraxis gene. Furthermore, TSCs were transfected with scleraxis knockdown or overexpression plasmids, and the results indicated that scleraxis plays a pivotal role in the differentiation of TSCs to tenocytes. In conclusion, dexamethasone inhibits the differentiation of TSCs to tenocytes by inhibiting the scleraxis gene.
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Neurology, Third Military Medical University, Chongqing 400038, China. Electronic address: zhangjqtmmu@yahoo.com.
authors.forename: Jiqiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: tangkanglai@hotmail.com.
authors.forename: Kanglai
authors.initials: K
authors.lastname: Tang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024042:Collagen Type I / Q000096:biosynthesis; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D005938:Glucocorticoids / Q000009:adverse effects; D008565:Membrane Proteins / Q000096:biosynthesis; D015735:Mifepristone / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology; D013708:Tendon Injuries / Q000139:chemically induced / Q000601:surgery*; D013710:Tendons / Q000166:cytology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D003907:Dexamethasone; D005938:Glucocorticoids; D008565:Membrane Proteins; D015735:Mifepristone; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C503819:Scx protein, rat; C486027:Tnmd protein, rat
keywords: Dexamethasone; Differentiation; Scleraxis; Tendon stem cells