Article

Chondroprotective effect of alendronate in a rabbit model of osteoarthritis.

Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan.
Journal of Orthopaedic Research (Impact Factor: 2.88). 04/2011; 29(10):1572-7. DOI: 10.1002/jor.21394
Source: PubMed

ABSTRACT The aim of this study was to determine how alendronate (ALN) alters cartilage degeneration and periarticular bone quality in a rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA). Thirty rabbits underwent an ACLT on the left knee and a sham operation on the right knee. Fifteen rabbits received weekly subcutaneous injections of ALN (0.14 mg/kg) and 15 rabbits (the control [cont] group) received saline. Animal knees were divided into four groups: cont/sham, cont/ACLT, ALN/sham, and ALN/ACLT. Histological, radiological, and immunohistochemical indices were evaluated for each group. Bone volume ratios by micro-computed tomography showed that ALN prevented periarticular bone loss. Histologically, the cont/ACLT group had significantly worse cartilage damage than the cont/sham group 12 weeks after the surgery. However, the ALN/ACLT group had mild cartilage degeneration compared with that of the ALN/sham group. Immunohistochemical analysis showed that ALN suppressed the expression of matrix metalloproteinase-13, interleukin-1β, type-X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor κB ligand in OA cartilage. ALN had a chondroprotective effect in an experimental rabbit model of OA.

0 Bookmarks
 · 
316 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionAngiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection.Methods First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group).ResultsHistologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group.Conclusions Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.
    Arthritis Research & Therapy 09/2014; 16(5):427. DOI:10.1186/s13075-014-0427-y · 4.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoarthritis (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-kappaB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated.
    BMC Musculoskeletal Disorders 11/2014; 15(1):370. DOI:10.1186/1471-2474-15-370 · 1.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although rose hip administration reduces pain and stiffness in patients with osteoarthritis, the mechanism of rose hip to alleviate primary symptoms has not been investigated. We examined how two types of Rosa canina, grown in Denmark (I-Flex) and Coesam in Chile, attenuate the osteoarthritis symptoms in male rats with osteoarthritis. Therefore pain-related behaviors were evaluated, and histological changes and cytokine expression in the articular cartilage of right knee induced osteoarthritis were assessed via intra-articular monoiodoacetate (MIA) injection. The right knee induced swollen knee, limping legs, and disproportional weight distribution into the right hind paw, and reduced maximum velocity to run on a treadmill from day 3 after MIA injection. The symptoms were exacerbated up to about 2 weeks and remained steady until day 21. Overall the osteoarthritis symptoms in MIA-injected control rats did not significantly change over the experimental period. After 21 days, bone mineral density in right leg and knee had greatly decreased in rats injected with MIA. These symptoms were related to increased expression of matrix metalloprotinase (MMP)-3 and MMP-13 in articular cartilage that degraded collage and elevated the production of TNF-α, IL-1β, and IL-6. However, both types of rose hip markedly attenuated all of the symptoms experienced by the control and overall symptoms from day 3 were improved at day 21. However, some symptoms of osteoarthrit remained and there was no difference between both rose hips for alleviating osteoarthritis symptoms. In conclusion, rose hips from Denmark and Coesam in Chile are potential therapeutic agents for the protection of articular cartilage against progression of osteoarthritis.
    Journal of the Korean Society for Applied Biological Chemistry 04/2014; 57(2):143-151. DOI:10.1007/s13765-014-4020-5 · 0.54 Impact Factor

Full-text (2 Sources)

Download
72 Downloads
Available from
May 17, 2014