title: Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing.
abstract: BACKGROUND
  This study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs). Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways. It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced osteoporotic fractures.
  
  
  METHODS
  Closed femoral fracture in SHAM and ovariectomized rats were used in this study. Weekly callus width (CW) and area (CA), endpoint mechanical properties, gene expressions of Col-1, BMP-2, ER-α, ER-β and ER-α:ER-β ratios (ER-ratios), and correlations were assessed at 2, 4 and 8 weeks post-fracture.
  
  
  RESULTS
  CW and CA results confirmed that OVX-induced osteoporotic fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties. Gene expressions of ER-α and ER-β were higher in the SHAM group at week 2 (p < 0.05) and later lowered at week 8; whereas the OVX group showed an opposing trend. Moderate correlation existed between ER-α and BMP-2 (0.545, p = 0.003), and ER-ratio and BMP-2 (0.601, p = 0.001), and BMP-2 to CW and CA (r = 0.709, p = 0.000 and r = 0.588, p = 0.001, respectively). ER-α and ER-β proteins expressions were confirmed by immunohistochemistry at the fracture callus in reparative progenitor cells, osteoblasts- and osteoclasts-like cells.
  
  
  CONCLUSIONS
  We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-β ratio favors callus formation.
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Chow
authors.forename: Kwok-Sui
authors.initials: KS
authors.lastname: Leung
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wei
authors.forename: Wing-Hoi
authors.initials: WH
authors.lastname: Cheung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002146:Bony Callus / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005264:Femoral Fractures / Q000209:etiology / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D005596:Fractures, Closed / Q000209:etiology / Q000378:metabolism; D058866:Osteoporotic Fractures / Q000209:etiology / Q000378:metabolism*; D010052:Ovariectomy; D011183:Postoperative Complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta