title: Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus.
abstract: OBJECTIVE
  Calcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) in normal and sCT over-expressing mice.
  
  
  METHODS
  Bone phenotype of transgenic (TG) C57Bl/6 mice over-expressing sCT at 6 months and 12 months was investigated by (1) serum osteocalcin and urinary deoxypyridinoline and (2) dynamic and normal histomorphometry of vertebrae bodies. In subsequent evaluation of cartilage and subchondral bone changes, 44 10-week old TG or wild-type (WT) mice were randomized into four groups and subjected to DMM or sham-operations. After 7 weeks animals were sacrificed, and knee joints were isolated for histological analysis.
  
  
  RESULTS
  Trabecular bone volume (BV/TV) increased 150% after 6 months and 300% after 12 months in sCT-expressing mice when compared to WT controls (P<0.05). Osteoblast number, bone formation rate and osteocalcin measurements were not affected in TG mice over-expressing sCT. In WT animals, a 5-fold increase in the quantitative erosion index was observed after DMM, and the semi-quantitative OARSI score showed over 400% (P<0.001) increase, compared to sham-operated WT mice. DMM-operated TG mice were protected against cartilage erosion and showed a 65% and 64% (P<0.001) reduction, respectively, for the two histopathological evaluation methods.
  
  
  CONCLUSIONS
  sCT over-expressing mice had higher bone volume, and were protected against cartilage erosion. These data suggest that increased levels of sCT may hamper the pathogenesis of osteoarthritis (OA). However more studies are necessary to confirm these preliminary results.
authors: Cartilage Biology and Biomarker R&D, Nordic Bioscience, Herlev, Denmark. bcs@nordicbioscience.com
authors: B C
authors: BC
authors: Sondergaard
authors: P
authors: P
authors: Catala-Lehnen
authors: A K
authors: AK
authors: Huebner
authors: A-C
authors: AC
authors: Bay-Jensen
authors: T
authors: T
authors: Schinke
authors: K
authors: K
authors: Henriksen
authors: S
authors: S
authors: Schilling
authors: M
authors: M
authors: Haberland
authors: R H
authors: RH
authors: Nielsen
authors: M
authors: M
authors: Amling
authors: M A
authors: MA
authors: Karsdal
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000473:pathology; D002116:Calcitonin / Q000502:physiology*; D002358:Cartilage, Articular / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010006:Osteoblasts / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology; D010641:Phenotype; D000070600:Tibial Meniscus Injuries
chemical_list: D001057:Apolipoproteins E; D015675:Osteocalcin; C028815:salmon calcitonin; D002116:Calcitonin