title: Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.
abstract: OBJECTIVE
  To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA).
  
  
  METHODS
  Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.
  
  
  RESULTS
  The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks.
  
  
  CONCLUSIONS
  The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.
authors: Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors: De-gang
authors: DG
authors: Yu
authors: Hui-feng
authors: HF
authors: Ding
authors: Yuan-qing
authors: YQ
authors: Mao
authors: Ming
authors: M
authors: Liu
authors: Bo
authors: B
authors: Yu
authors: Xin
authors: X
authors: Zhao
authors: Xiao-qing
authors: XQ
authors: Wang
authors: Yang
authors: Y
authors: Li
authors: Guang-wang
authors: GW
authors: Liu
authors: Shao-bo
authors: SB
authors: Nie
authors: Shen
authors: S
authors: Liu
authors: Zhen-an
authors: ZA
authors: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008592:Menisci, Tibial / Q000187:drug effects* / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D000070600:Tibial Meniscus Injuries; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D055758:SOX9 Transcription Factor; D013876:Thiophenes; C081587:strontium ranelate