Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis

Hirayama, T; Danks, L; Sabokbar, A; Athanasou, N A

doi:10.1093/rheumatology/41.11.1232

Cited by 112 publications

(88 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increased osteoclast activity is seen in many osteopenic disorders, including postmenopausal osteoporosis [1,2], Paget's disease [3,4], bone metastases [5,6], periodontitis [7,8], and rheumatoid arthritis [9,10]. Mature osteoclasts are giant, multinucleated cells that synthesize and directionally secrete bone matrix-degrading enzymes, including cathepsin K, matrix metalloproteinase-9 (MMP9), and tartrate-resistant acid phosphatase (TRAP).…”

Section: Introductionmentioning

confidence: 99%

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Cronstein

2012

Purinergic Signalling

View full text Add to dashboard Cite

Adenosine is an endogenous nucleoside that modulates many physiological processes through four receptor subtypes (A 1 , A 2a , A 2b , A 3 ). Previous work from our laboratory has uncovered a critical role for adenosine A 1 receptor (A 1 R) in osteoclastogenesis both in vivo and in vitro. Our current work focuses on understanding the details of how A 1 R modulates the receptor activator of NF-κB ligand (RANKL)-induced signaling in osteoclastogenesis. Osteoclasts were generated from mouse bone marrow precursors in the presence of RANKL and macrophage-colony stimulating factor. A pharmacological antagonist of A 1 R (DPCPX) inhibited RANKL-induced osteoclast differentiation, including osteoclast-specific genes (Acp5, MMP9, β 3 Integrin, α v Integrin, and CTSK) and osteoclast-specific transcription factors such as c-fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression in a dose-dependent manner. DPCPX also inhibited RANKL-induced activation of NF-κB and JNK/ c-Jun but had little effect on other mitogen-activated protein kinases (p38 and Erk). Finally, immunoprecipitation analysis showed that blockade of A 1 R resulted in disruption of the association of tumor necrosis factor receptor-associated factor 6 (TRAF6) and transforming growth factor-β-activated kinase 1 (TAK1), a signaling event that is important for activation of NF-κB and JNK, suggesting the participation of adenosine/ A 1 R in early signaling of RANKL. Collectively, these data demonstrated an important role of adenosine, through A 1 R in RANKL-induced osteoclastogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Cronstein

2012

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…BMD loss in RA is primarily thought to be the effect of increased osteoclast activity (8) and to a lesser extent the effect of impairment of bone formation by osteoblasts (9). With high disease activity, levels of inflammatory media-tors such as tumor necrosis factor ␣ (TNF␣), interleukin-1 (IL-1), IL-6, and IL-17 are high (10 -18).…”

Section: Introductionmentioning

confidence: 99%

Changes in hand bone mineral density and the association with the level of disease activity in patients with rheumatoid arthritis: Bone mineral density measurements in a multicenter randomized clinical trial

Dirven

Güler‐Yüksel

Beus

et al. 2011

Arthritis Care & Research

View full text Add to dashboard Cite

Objective. To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. Methods. mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 > DAS < 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified. Results. Mean change in mBMD in CR patients was ؊0.03%, compared to ؊3.13% and ؊2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to ؊4.6 mg/cm 2 /year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (>4.6 mg/cm 2 /year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0 -18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain. Conclusion. In RA, mBMD gain occurs primarily in patients in continuous (>1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.

show abstract

“…3 Bone erosion causes distal diaphysis of tibia and tarsal bones located near ankle joints with severe arthritis, suggesting that infiltration of inflammatory cells into adjacent bone tissues triggers extensive osteoclastogenesis. 4 How-ever, only limited information has so far been available concerning the recruitment of abundant osteoclasts in the site of severe bone destruction. Osteoclastogenesis occurs in the bone marrow cavity from the hematopoietic stem cells present in the bone marrow.…”

mentioning

confidence: 99%

“…5 Excessive osteoclastogenesis induced by these cytokines often triggers pathological bone destruction at particular bone sites. 4 Receptor activator nuclear factor k B ligand (RANKL), believed to be the most important cytokine for normal osteoclastogenesis, is also involved in inflammatory bone resorption. 6 In addition to cytokines being involved in osteoclastogenesis, an involvement of factors bearing the ability of chemotaxis against cells in the osteoclast lineage should be considered.…”

mentioning

confidence: 99%

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Toh

Kukita

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

In the rat model of rheumatoid arthritis, a marked formation of osteoclasts is found in the distal tibia and the metatarsal bone. It was therefore postulated that osteoclast progenitors would be increased in the bone marrow cavities of rats with adjuvant-induced arthritis (AA rats). Bone marrow cells obtained from tibia of AA rats were cultured to form cells in the osteoclast lineage to access the number of osteoclast progenitors. Unexpectedly, only a suppressed level of osteoclast progenitors was detected in the diaphyseal bone marrow of tibia in AA rats. Distribution of osteoclast progenitors in the bone marrow cavity was examined, and it was shown that osteoclast progenitors accumulated in the distal tibia. Macrophage inflammatory protein (MIP)-1a, an osteoclastogenic CC chemokine, was expressed in ED-1-positive macrophages localizing in the distal tibia with marked bone destruction. Chemotaxis studies showed that MIP-1a expressed significant activity towards bone marrow cells. The suppressed level of osteoclastogenesis in bone marrow cells of AA rats was restored to a normal level by the addition of MIP-1a. It was suggested that MIP-1a is involved in the migration of osteoclast progenitors to the distal tibia as well as in osteoclastogenesis in AA rats. In these rats, in situ hybridization of the distal tibia with a high level of bone destruction showed significant expression of Receptor activator nuclear factor jB ligand (RANKL) messenger RNA in aggregates of multinucleated osteoclast-like cells present in the bone marrow cavity, a unique pathological feature for these rats. Migrated osteoclast progenitors are thought to be efficiently differentiated into osteoclasts in response to RANKL expressed by the aggregates of osteoclastlike cells under the influence of the MIP-1a. Such positive-feedback regulation of osteoclastogenesis could result in the highest recruitment of active osteoclasts in the area of marked bone destruction.

show abstract

Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis

Cited by 112 publications

References 34 publications

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Changes in hand bone mineral density and the association with the level of disease activity in patients with rheumatoid arthritis: Bone mineral density measurements in a multicenter randomized clinical trial

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Contact Info

Product

Resources

About