Document Detail


Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.
MedLine Citation:
PMID:  23334238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: 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.
CONCLUSION: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.
Authors:
De-gang Yu; Hui-feng Ding; Yuan-qing Mao; Ming Liu; Bo Yu; Xin Zhao; Xiao-qing Wang; Yang Li; Guang-wang Liu; Shao-bo Nie; Shen Liu; Zhen-an Zhu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-21
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  34     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-05     Completed Date:  2013-12-27     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  United States    
Other Details:
Languages:  eng     Pagination:  393-402     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Bone Density Conservation Agents / administration & dosage,  therapeutic use*
Bone Remodeling / drug effects*
Chondrocytes / drug effects,  pathology
Disease Models, Animal
Dose-Response Relationship, Drug
Immunohistochemistry
In Situ Nick-End Labeling
Male
Menisci, Tibial / drug effects*,  injuries,  pathology
Osteoarthritis / drug therapy*,  etiology,  pathology
Rats
Rats, Sprague-Dawley
SOX9 Transcription Factor / metabolism
Spectrum Analysis, Raman
Thiophenes / administration & dosage,  therapeutic use*
Time Factors
Chemical
Reg. No./Substance:
0/Bone Density Conservation Agents; 0/SOX9 Transcription Factor; 0/Thiophenes; 04NQ160FRU/strontium ranelate

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