Abstract

BackgroundOsteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated.Methods60 New Zealand rabbits were randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the 4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 and 14 weeks, respectively. Trabecular characteristics and cartilage changes were detected using Micro-CT, safranin O and rapid green staining, respectively. Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, MMP-9 and TLR-4 expression was evaluated by western blot analysis.ResultsMicro-CT and histology analyses indicated that PAM treatment for 2 or 10 weeks could completely prevent or reverse osteoarthritic subchondral bone loss and cartilage surface erosion. Immunohistochemistry and western blot analysis indicated that expression of OPG and RANKL increased, although RANKL expression increased more significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM group was significantly higher than that in the ACLT group. Additionally, expression of MMP-9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM treated groups.ConclusionsPAM can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-370) contains supplementary material, which is available to authorized users.

Highlights

  • Osteoarthritis (OA) is a major health problem in the increasingly elderly population

  • At 4 weeks after model establishment, Bone volume fraction (BV/TV) and Trabecular thickness (TbTh) were both significantly lower (P

  • After 2 weeks of treatment, the pamidronate disodium (PAM) group showed significantly increased BV/TV, Trabecular number (TbN) and TbTh compared with the anterior cruciate ligament transection (ACLT) group (P

Read more

Summary

Introduction

Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilaginous degeneration, osteophyte formation, subchondral bone changes and synovial inflammation [1,2]. Thereafter, multiple reports have suggested that changes in subchondral bone may alter the load distribution, and so becoming an important inducing or accelerating cause for cartilaginous injury in OA [3,6,7]. Recent animal experiments have shown that early-stage OA is accompanied by a reduction in bone volume, indicating that the initial subchondral bone resorption may be a crucial factor for OA onset and progression [8,9]. Determining the exact effects of subchondral bone on the occurrence and development of OA, during the early stage, is of crucial importance in seeking new diagnostic markers and therapeutic targets for OA [2,4]

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call