title: Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig.
abstract: BACKGROUND
  Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs.
  
  
  METHODS
  Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing.
  
  
  RESULTS
  Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and elastic modulus increased from 3 to 6 months old and thereafter maintained in a stable level, which were enhanced by CT treatment.
  
  
  CONCLUSIONS
  Pretreatment with CT could prevent naturally occurring intervertebral disc degeneration in guinea pigs, which might be related to the modulation of extracellular matrix metabolism and the integrity and biomechanical properties in adjacent vertebral body.
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University Shijiazhuang 050017, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Medical Research Center, Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Faming
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University Shijiazhuang 050017, People's Republic of China.
authors.forename: Jinyin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Huanjiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University Shijiazhuang 050017, People's Republic of China.
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University Shijiazhuang 050017, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University Shijiazhuang 050017, People's Republic of China ; Department of Orthopedic Surgery, Affiliated Hospital of Hebei United University Tangshan 063000, Hebei Province, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
keywords: Calcitonin; Micro-CT; biomechanics; guinea pig; intervertebral disc degeneration