RANK ligand, RANK, and OPG expression in type II collagen-induced arthritis mouse

Mori, Hiroyuki; Kitazawa, Riko; Mizuki, Shinichi; Nose, Masato; Maeda, Sakan; Kitazawa, Sohei

doi:10.1007/s00418-001-0376-9

Cited by 50 publications

(22 citation statements)

References 37 publications

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“…Although cartilage loss was also reduced by OPG, the effects on cartilage were again lower than those on bone (48). Similar to this rat model, it has been recently suggested that the RANKL-RANK system plays an important role in osteoclastogenesis in both local and systemic osteolytic lesions in autoimmune type II collagen-induced arthritis in mice (49). These studies provide evidence for the role of osteoclasts (and of RANKL) in the pathogenesis of bone erosion in arthritis in several animal models of arthritis with distinct pathogenetic mechanisms.…”

Section: Rankl and Arthritissupporting

confidence: 71%

RANK, RANKL and osteoprotegerin in arthritic bone loss

Bezerra

Carvalho

Prokopowitsch

et al. 2005

Braz J Med Biol Res

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Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL) released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1), IL-6, IL-11, IL-17, tumor necrosis factor-α, prostaglandin E 2 , or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

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Section: Rankl and Arthritissupporting

confidence: 71%

RANK, RANKL and osteoprotegerin in arthritic bone loss

Bezerra

Carvalho

Prokopowitsch

et al. 2005

Braz J Med Biol Res

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“…Similarly, in type II collagen-induced arthritis in mice, RANK/RANKL plays an important role in osteoclastogenesis in local and systemic osteolytic lesions (64). This process may be driven by human RA inflammatory cells that express RANKL, whereas OPG is not detectable in the same setting (18).…”

Section: Animal Modelsmentioning

confidence: 99%

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Neumann

Müller‐Ladner

2005

Arthritis & Rheumatism

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“…Increased osteoclast activity has been reported in many osteopenic disorders, including postmenopausal osteoporosis, Paget's disease, bone metastases, and rheumatoid arthritis (5)(6)(7). TRANCE interacts with two receptors: a secreted decoy receptor osteoprotegerin, OPG (8), and a transmembrane receptor, RANK (9 -11).…”

Section: Trancementioning

confidence: 99%

Disabling of Receptor Activator of Nuclear Factor-κB (RANK) Receptor Complex by Novel Osteoprotegerin-like Peptidomimetics Restores Bone Loss in Vivo

Cheng

Kinosaki

Miki

et al. 2004

Journal of Biological Chemistry

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The tumor necrosis factor family ligand, tumor necrosis factor-related activation-induced cytokine (TRANCE), and its receptors, receptor activator of nuclear factor-B (RANK) and osteoprotegerin (OPG), are known to be regulators of development and activation of osteoclasts in bone remodeling. Sustained osteoclast activation that occurs through TRANCE-RANK causes osteopenic disorders such as osteoporosis and contributes to osteolytic metastases. Here, we report a rationally designed small molecule mimic of osteoprotegerin to inhibit osteoclast formation in vitro and limit bone loss in an animal model of osteoporosis. One of the mimetics, OP3-4, significantly inhibited osteoclast formation in vitro (IC 50 ‫؍‬ 10 M) and effectively inhibited total bone loss in ovariectomized mice at a dosage of 2 mg/kg/day. Unlike soluble OPG receptors, which preclude TRANCE binding to RANK, OP3-4 shows the ability to modulate RANK-TRANCE signaling pathways and alters the biological functions of the RANK-TRANCE receptor complex by facilitating a defective receptor complex. These features suggest that OPG-derived small molecules can be used as a probe to understand complex biological functions of RANK-TRANCE-OPG receptors and also can be used as a platform to develop more useful therapeutic agents for inflammation and bone disease. TRANCE,1 a TNF family member, also known as OPGL, RANKL, ODF, and OCIF, plays a key role in the development of osteoclasts and in modulating their bone resorbing activity (1-4). Increased osteoclast activity has been reported in many osteopenic disorders, including postmenopausal osteoporosis, Paget's disease, bone metastases, and rheumatoid arthritis (5-7). TRANCE interacts with two receptors: a secreted decoy receptor osteoprotegerin, OPG (8), and a transmembrane receptor, RANK (9 -11). The interaction between TRANCE and RANK is essential for osteoclastogenesis because RANK is activated by TRANCE and then associates with TNF receptorassociated family members to trigger downstream signaling (11) events. OPG, on the other hand, plays an opposite role by preventing TRANCE from binding and activating RANK and thus is considered a "decoy" receptor. In this way, the interaction between TRANCE and OPG or TRANCE and RANK represents a complex network required for normal bone development, and any imbalance in the system potentially leads to bone disorders. Thus it is well recognized that this receptor complex network is an interesting drug development target for the treatment of bone disorders such as osteoporosis (12), and there is considerable interest in developing ways to modulate RANK functions which may prove beneficial for bone-related pathologies.To date there is no three-dimensional structural information available for the RANK receptor complex. However, it is believed that the complex should resemble that of the TNF receptor as a member of TNF superfamily. The TNF-␤⅐TNFR1 co-crystal structure has been solved, thus facilitating rational drug design based on the receptor-ligand interaction sites coupled wi...

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RANK ligand, RANK, and OPG expression in type II collagen-induced arthritis mouse

Cited by 50 publications

References 37 publications

RANK, RANKL and osteoprotegerin in arthritic bone loss

RANK, RANKL and osteoprotegerin in arthritic bone loss

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Disabling of Receptor Activator of Nuclear Factor-κB (RANK) Receptor Complex by Novel Osteoprotegerin-like Peptidomimetics Restores Bone Loss in Vivo

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