title: The response of cells derived from the supraspinatus tendon to estrogen and calciotropic hormone stimulations: in vitro study.
abstract: OBJECTIVE
  The most frequent complications after rotator cuff repair (RCR) are non-healing and re-tear. Age and gender are both proven risk factors for faulty RCR. This study analyzed the effects of female sex steroids and calciotropic hormones on tendon-derived cell characteristics.
  
  
  METHODS
  Tendon-derived cells from rat supraspinatus were treated with estradiol-17β (E2); soy isoflavones (daidzein, genistein, biochainin A); raloxifene and estrogen receptors α and β agonists and antagonists; and less-calcemic vitamin-D analog, parathyroid hormone, and vehicle control for 24 h. Cell proliferation and mRNA expression of estrogen receptor α and β, vitamin-D receptor (VDR), scleraxis, and collagen-1 were assessed.
  
  
  RESULTS
  E2, Biochainin A, raloxifene, and vitamin-D significantly increased tendon-derived cell proliferation. Estrogen receptor α antagonists neutralized tendon-derived cells response to estradiol 17-β; however, estrogen receptor β antagonists did not have an effect. Scleraxis expression decreased following estradiol 17-β and vitamin-D treatments. Vitamin-D significantly reduced collagen-1 expression, while estradiol 17-β had no effect. Vitamin-D and estradiol 17-β upregulated VDR expression.
  
  
  CONCLUSIONS
  Significant tendon-derived cell proliferation can be achieved with commonly prescribed female sex and calciotropic hormones. However, collagen-1 expression remained constant or decreased following the administration of these hormones. Female sex steroids and vitamin-D promoted tendon-derived cell proliferation via estrogen receptor α and VDR, not estrogen receptor β. Amplified cell proliferation was not associated with increased scleraxis and collagen-1 expression. These results have important implications to the properties of healing tendon and possible pharmaceutical therapies for patients with torn RC. Further research is warranted to expose the underling mechanisms of these effects.
authors.affiliation: a Shoulder Unit, Division of Orthopedic Surgery, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Maman
authors.affiliation: b Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Dalia
authors.initials: D
authors.lastname: Somjen
authors.affiliation: c IVF unit, Department of Obstetrics and Gynecology , Sheba Medical Center, Tel Hashomer, Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Ettie
authors.initials: E
authors.lastname: Maman
authors.affiliation: b Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Katzburg
authors.affiliation: a Shoulder Unit, Division of Orthopedic Surgery, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Sharfman
authors.affiliation: b Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
authors.affiliation: a Shoulder Unit, Division of Orthopedic Surgery, Tel-Aviv Medical Center and the Sackler Faculty of Medicine , Tel-Aviv University , Tel-Aviv , Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Dolkart
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004967:Estrogens / Q000819:agonists / Q000494:pharmacology*; D005260:Female; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism; D017006:Rotator Cuff / Q000166:cytology*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D004247:DNA; D004967:Estrogens; D018167:Receptors, Calcitriol; D014807:Vitamin D; C503819:Scx protein, rat
keywords: Calciotropic hormones; cell proliferation; estrogen receptors; estrogens; tendon-derived cells