The Increase of Parathyroid Hormone-Related Peptide and Cytokine Levels in Synovial Fluid of Elderly Rheumatoid Arthritis and Osteoarthritis.

Horiuchi, Toshiyuki; Yoshida, Tsuyoshi; Kinoshita, Yasuko; Sakamoto, Hiroshi; Kanai, Hiroyuki; Yamamoto, Seiji; Ito, Hideki

doi:10.1507/endocrj.46.643

Cited by 45 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The strong correlation we found between synovial fluid IL-18 and TNFα is consistent with these reports. The concentration of synovial fluid TNFα we found in our subjects was similar to previous reports for OA synovial fluid and approximately sixfold lower than has been reported for RA (34,35). Although we found a strong correlation of TNFα with uric acid concentration and OA severity, the lower levels of TNFα when compared with RA, along with the correspondingly lower IL-18, suggest a less acute inflammatory process driven by IL-18 as part of an innate immune response.…”

Section: Discussionsupporting

confidence: 88%

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Denoble¹,

Huffman²,

Stäbler³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

236

178

View full text Add to dashboard Cite

Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1β. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1β was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1β) known to be produced by uric acidactivated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.arthritis | inflammation | interleukin-18 | interleukin-1β | tumor necrosis factor alpha U ric acid (UA) is constitutively present in normal cells, increased in concentration when cells are injured, and released from dying cells (1). On the basis of a theory proposed by Matzinger, the products of cell stress and tissue damage may represent "danger signals" that function as endogenous adjuvants recognized by the immune system (2). Matzinger proposed that immunity is controlled by an internal conversation between tissues and the cells of the immune system (3). This proposal introduced a new immunological model of an immune system capable of sensing cellular stress and tissue damage (4). Shi subsequently identified uric acid as one of these principal endogenous danger signals released from injured cells and mediating the immune response to antigens associated with injured cells (1). The molecular mechanism of this innate immune response to uric acid was further shown to be the result of the activation of the NALP3 inflammasome, a cytosolic, multiprotein complex that mediates caspase activation by uric acid crystals, leading to the production of the active forms of IL-1β and IL-18 (5). Recently, Kono et al. demonstrated in an in vivo hepatoxicity mouse model that uric acid is a physiological regulator of the inflammation induced by tissue injury (6). These data form the basis for our hypothesis that synovial fluid uric acid is a factor regulating tissue inflammation, disease severity, and progression in osteoarthritis (OA).Uric acid is best known for its role in gout. When uric acid concentrations exceed the limit of solubility (∼6.8 mg/dL or even lower under conditions of low pH or temperature), crystal formation can ensue, which is capable of activating the NALP3 inflammasome (5) and triggering the acute severe attacks of joint inflammation characteristic of gout (7). Several studies have previously posited an association o...

show abstract

Section: Discussionsupporting

confidence: 88%

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Denoble¹,

Huffman²,

Stäbler³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

236

178

View full text Add to dashboard Cite

show abstract

“…In pathological states accompanied by bone loss such as osteoporosis, periodontal disease and rheu-matoid arthritis, recent attention has been focused on cytokines including interleukin-1 (IL-1) generated in the bone microenvironment that may be responsible for stimulating osteoclastic bone resorption [10,11]. Several studies suggested that increased IL-1 production by human peripheral blood mononuclear cells (PBMCs) is responsible for development of osteoporosis [12,13].…”

Section: Osteoclastsmentioning

confidence: 99%

Interleukin-1.BETA. Stimulates Transendothelial Mobilization of Human Peripheral Blood Mononuclear Cells with a Potential to Differentiate into Osteoclasts in the Presence of Osteoblasts.

et al. 2001

View full text Add to dashboard Cite

Abstract.There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated.We present here additional evidence that IL-19 enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-l jl stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones.These findings provide circumstantial evidence for the hypothesis that IL-19 generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.

show abstract

“…More recently, PTHrP has also been identified as a member of the cascade of cytokines produced in prodigious amounts by the rheumatoid synovium (5,6). As with other cytokines, PTHrP is expressed by synoviocytes, the primary cell comprising the tumor-like rheumatoid synovium (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

“…As with other cytokines, PTHrP is expressed by synoviocytes, the primary cell comprising the tumor-like rheumatoid synovium (5)(6)(7)(8)(9). TNF␣ and IL-␤, 2 key inflammatory cytokines in RA, induce synoviocyte PTHrP expression, and PTHrP, in turn, induces synoviocyte secretion of IL-6 (5).…”

mentioning

confidence: 99%

Blockade of parathyroid hormone–related protein prevents joint destruction and granuloma formation in streptococcal cell wall–induced arthritis

Funk¹,

Chen²,

Downey³

et al. 2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To determine whether parathyroid hormone-related protein (PTHrP), an interleukin-1␤-inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA.Methods. PTHrP expression and the effect of PTHrP 1-34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW)-induced arthritis, an animal model of RA.Results. As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor-positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1-34.Conclusion. These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders.

show abstract

The Increase of Parathyroid Hormone-Related Peptide and Cytokine Levels in Synovial Fluid of Elderly Rheumatoid Arthritis and Osteoarthritis.

Cited by 45 publications

References 18 publications

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Interleukin-1.BETA. Stimulates Transendothelial Mobilization of Human Peripheral Blood Mononuclear Cells with a Potential to Differentiate into Osteoclasts in the Presence of Osteoblasts.

Blockade of parathyroid hormone–related protein prevents joint destruction and granuloma formation in streptococcal cell wall–induced arthritis

Contact Info

Product

Resources

About