Osteoclasts: Culprits in inflammatory osteolysis

Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St Louis, MO 63110, USA.
Arthritis research & therapy (Impact Factor: 3.75). 02/2006; 8(1):201. DOI: 10.1186/ar1857
Source: PubMed


Periarticular osteolysis, a crippling complication of rheumatoid arthritis, is the product of enhanced osteoclast recruitment and activation. The osteoclast, which is a member of the monocyte/macrophage family, is the exclusive bone resorptive cell, and its differentiation and activation are under the aegis of a variety of cytokines. Receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor are the essential osteoclastogenic cytokines and are increased in inflammatory joint disease. Tumor necrosis factor-alpha, which perpetrates arthritic bone loss, exerts its osteoclastogenic effect in the context of RANKL with which it synergizes. Achieving an understanding of the mechanisms by which the three cytokines affect the osteoclast has resulted in a number of active and candidate therapeutic targets.

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Available from: Steven Teitelbaum, Sep 22, 2014
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    • "Actin ring is a distinctive cytoskeletal structure in mature osteoclasts, and its formation is essential for osteoclastic bone resorption [19]. Osteoclasts formed a ring-like F-actin structure, actin ring, at the cell periphery on tissue culture plates. "
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    ABSTRACT: The rhizome of Dryopteris crassirhizoma has been used as a traditional herbal medicine for treating various inflammatory and infectious diseases such as tapeworm infestation and mumps. In the present study, we investigated the bone protective effect of water extract of the rhizome of Dryopteris crassirhizoma (WEDC). We found that WEDC inhibits osteoclast differentiation via directly acting on osteoclast precursors. In osteoclast precursors, WEDC inhibited receptor activator of nuclear factor- κ B ligand- (RANKL-) induced expression of c-Fos and nuclear factor of activated T cells cytoplasmic 1, a key downstream target of c-Fos during osteoclast differentiation. We found that WEDC inhibits RNAKL-induced activation of extracellular-regulated kinase and NF- κ B that mediates c-Fos expression and osteoclast differentiation. In addition to the inhibitory effect of osteoclast differentiation, WEDC markedly suppressed bon-resorbing activity of mature osteoclasts, which was accompanied by disruption of actin ring structure. Furthermore, administration of WEDC suppressed RANKL-induced trabecular bone loss in mice. Collectively, our results demonstrate that WEDC inhibits not only osteoclast differentiation by inhibiting RANK signaling pathways in osteoclast precursors but also bone resorption by disrupting actin ring in mature osteoclasts, thereby contributing to its protective effect on bone loss.
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    • "TNF-α exerts its biological effects by binding to TNF type 1 receptor (TNF-R1) and type 2 receptor (TNF-R2) [20, 21]. Both receptors are expressed in the lineages of osteoclasts and osteoblasts [22]. TNF-α plays a central role for inflammatory reaction [23, 24]. "
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    ABSTRACT: Purpose Bisphosphonates (BPs) are antiresorptive drugs that provide important effects on bone turnover. The key to the high efficiency of BPs is their affinity for bone tissue, and their chemical structure provides their molecular mechanism of action. BPs are widely used to treat a variety of diseases that cause excess bone resorption, such as bone metastasis, hypercalcaemia due to malignancy and Paget’s disease. The goal of this study was to assess whether the bisphosphonate (Pamifos®) present in bone cement has any effect on bone turnover. In this paper, we present changes in cytokine levels in the serum of rats treated surgically. Methods Research was performed on 40 adult male Wistar rats. The rats were divided into four groups: two control groups (A, B) and two experimental groups (C, D). Bone in rats in the experimental groups was implanted with BP-enriched cement, whereas bone in control-groups rats was implanted with clean cement (without BPs). Results We found a higher concentration of tumour necrosis factor alpha (TNF-α) three weeks after surgery in rats implanted with BP-enriched cement compared with rats implanted with clean cement. After six weeks of treatment, TNF-α levels decreased significantly in rats treated with BP-enriched cement, whereas the control group experienced an increase in TNF-α. The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. We found high levels of receptor activator of nuclear factor kappa-B ligand (RANKL) in rats after implantation of cement without BP in both groups. Conclusions We conclude that use of bisphosphonate (Pamifos®), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Therefore, the use of BP-enriched cement implants appears to be justified.
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    • "3–5). RANKL is a soluble, osteoblast-derived protein that induces bone resorption through osteoclast differentiation and activation (Teitelbaum, 2006). RANKL expression is induced in osteoblasts/ mesenchymal cells by a bone resorption factor (Yasuda et al., 1998). "
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