Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease

Strassle, Brian W.; Mark, Lilly; Leventhal, Liza; Piesla, Michael J.; Li, X. Jian; Kennedy, Jeffrey D.; Glasson, S.S.; Whiteside, Garth T.

doi:10.1016/j.joca.2010.06.007

Cited by 115 publications

(134 citation statements)

References 49 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…This aggravates the degenerative process, resulting in irreversible physical damage to cartilage, and gradually involves the whole joint with increase in the severity of OA (29). Besides this, inflammation attracts immune cells and osteoclast precursors, thereby increasing osteoclast formation and bone resorption in subchondral region (32). Various studies have shown that proinflammatory cytokines affect survival and phenotype of chondrocytes in several ways.…”

Section: Discussionmentioning

confidence: 99%

IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice

Kour

Garimella

Shiroor

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Osteoarthritis (OA) is a chronic disease of articular joints that leads to degeneration of both cartilage and subchondral bone. These degenerative changes are further aggravated by proinflammatory cytokines including IL-1β and TNF-α. Previously, we have reported that IL-3, a cytokine secreted by activated T cells, protects cartilage and bone damage in murine models of inflammatory and rheumatoid arthritis. However, how IL-3 protects cartilage degeneration is not yet known. In this study, we investigated the role of IL-3 on cartilage degeneration under both in vitro and in vivo conditions. We found that both mouse and human chondrocytes show strong expression of IL-3R at gene and protein levels. IL-3 increases the expression of mouse chondrocyte-specific genes, Sox9 and collagen type IIa, which were downregulated by IL-1β. Moreover, IL-3 downregulated IL-1β– and TNF-α–induced expression of matrix metalloproteinases in both mouse and human chondrocytes. Interestingly, IL-3 reduces the degeneration of articular cartilage and subchondral bone microarchitecture in a mouse model of human OA. Moreover, IL-3 showed the preventive and therapeutic effects on cartilage degeneration induced by IL-1β in micromass pellet cultures of human mesenchymal stem cells. Thus, to our knowledge, we provide the first evidence that IL-3 has therapeutic potential in amelioration of degeneration of articular cartilage and subchondral bone microarchitecture associated with OA.

show abstract

Section: Discussionmentioning

confidence: 99%

IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice

Kour

Garimella

Shiroor

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Changes in weightbearing asymmetry were evaluated one day before and once a week after OA induction. The percentage of weight placed on the right hind limb was determined using the formula below [28] .…”

Section: Pain Behavior Testingmentioning

confidence: 99%

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Mao

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. Methods: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 μg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. Results: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. Conclusion: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

show abstract

“…Several groups of investigators have demonstrated that bisphosphonates show promise for cartilage preservation to a degree [4,17,18]. A recent preclinical study demonstrated that ‘pre-emptive chronic’ bisphosphonate treatment increased bone mineral density (BMD) and was chondroprotective in rat models of joint degeneration.…”

Section: Introductionmentioning

confidence: 99%

Changes in Serum Levels of Cartilage Oligomeric Matrix Protein after Estrogen and Alendronate Therapy in Postmenopausal Women

Seo

Yang²,

Lim³

et al. 2012

Gynecol Obstet Invest

View full text Add to dashboard Cite

Background: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint destruction and its serum levels are used for assessing therapeutic efficacy. This study aims to compare changes in serum COMP levels in postmenopausal women with osteopenia/osteoporosis receiving estrogen and alendronate. Methods: A total of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated with either estrogen (17β-estradiol 1 mg, n = 30) or bisphosphonate (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and after 6 months of treatment. Results: Estrogen decreased levels of COMP at 6 months compared to baseline levels (–8.35 ± 19.38%), whereas the bisphosphonate and control groups resulted in no significant changes (–5.50 ± 18.69 and –1.49 ± 25.34%, respectively). Concentrations of osteocalcin decreased significantly in both treatment groups (estrogen –25.60 ± 24.42% and alendronate –13.76 ± 23.89%, respectively). There was a significant positive correlation between changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002). Conclusions: Postmenopausal women treated with estrogen showed significantly decreased levels of COMP after 6 months. Estrogen might provide a further treatment modality in the prevention of joint destruction.

show abstract

Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease

Abstract: Subchondral bone remodeling plays an important role in nociception and the pathobiology of the MIA model with osteoclasts being implicated in both bone and cartilage resorption. Inhibition of osteoclastic activity when initiated early leads to improved efficacy.

Cited by 115 publications

References 49 publications

IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice

IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Changes in Serum Levels of Cartilage Oligomeric Matrix Protein after Estrogen and Alendronate Therapy in Postmenopausal Women

Contact Info

Product

Resources

About