Sex steroids, such as estrogen and testosterone inhibit osteoclast differentiation by reducing expression of rankl or increasing the expression of opg, thus reducing resorption mundy, 1999. Radix paeoniae rubra stimulates osteoclast differentiation. B ligand rankl is a key cytokine that stimulates the osteoclast precursor cells to fuse and undergo differentiation into osteoclasts 7, 8. As rap1 is the effector of the campbinding epac protein exchange protein directly activated by camp, we determined the role of epac1 in osteoclast differentiation. Apr 23, 2018 radix paeoniae rubra rpr, a traditional chinese herb, has antiinflammatory and immunoregulatory properties. Some genes act during the formation andor survival of the osteoclast precursor cell pu. Aspirin treatment also had favorable therapeutic effects on bone regeneration in the bone defect model, and the number of osteoclasts was decreased. The mechanisms whereby arthritogenic organisms may induce cartilage and bone erosions in infectiontriggered arthritis remain unknown. Dendritic cells dcs, the most potent antigenpresenting cells, can also transdifferentiate into active ocs in the presence of receptor activator of nuclear factor.
Osteoclast differentiation and function multifunctional regulator in. Selective regulation of mapk signaling mediates rankl. Dl suppressed osteoclast differentiation by reducing the expression of the nuclear factor of activated tcells, cytoplasmic 1. Radix paeoniae rubra rpr, a traditional chinese herb, has antiinflammatory and immunoregulatory properties. Cells of the mylomonocytic lineage appropriate sources for in vitro differentiation are cells from bone marrow, monocytes, spleen or raw 264. Synovial fibroblasts infected with salmonella enterica.
Mmp stimulates osteoclast differentiation and activation. B and p38 map kinase, elevation of calcium levels, and induction of cfos are essential for osteoclast differentiation 2,3. The signal transduction pathways operating in osteoclastogenesis have been extensively studied. Forced expression of srankl in runx2 livers increased the number and size of osteoclastlike cells around calcified cartilage, although vascular invasion into the cartilage was superficial because of incomplete osteoclast differentiation. This function is critical in the maintenance, repair, and remodelling of bones of the vertebral skeleton.
Sep 29, 2000 tumor necrosis factor receptor family member rank mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Rank is the receptor for rankl and its role in osteoclast differentiation and activation is well established in vitro, as well as in mice and in humans 15, 2628. Osteoclast differentiation and activation request pdf. Blimp1mediated repression of negative regulators is required. Osteoclast differentiation and function are crucial for maintaining bone homeostasis and preserving skeletal integrity. This study explored the effects of rpr on stimulation of osteoclast differentiation in raw264. B ligand regulate osteoclast differentiation and activity. Osteoclast derivation from mouse bone marrow protocol. Dc osteoclast differentiation was modulated by aspirin via the nuclear factor kappa b nf.
Characterization of the osteoclast lineage cells in these mice provided important information on the stage of differentiation affected fig. The effects of lycii radicis cortex on ranklinduced. To date, little investigation on the relationship between ecm components and osteoclast differentiation. An osteoclast from ancient greek osteon, meaning bone, and. Dehydrocostus lactone suppresses osteoclast differentiation. Jul 17, 2019 tlr 2, 4, 5, and 9 are also expressed on osteoblasts and their activation increases osteoclast differentiation by an indirect mechanism through stimulation of rankl. Discovery of the rank signalling pathway in the osteoclast has. We are beginning to understand how extracellular stimuli through intracellular signalling lead to the expression and activation of key transcription factors.
In this study, we show that the mek5erk5 pathway participates in osteoclast differentiation. Stimulation of receptor activator of nuclear factor. Activation of trpv4 promotes osteoclasts differentiation. The binding of rank with rankl triggers a cascade of intracellular events that are essential to completing osteoclast differentiation and activation.
Tumor necrosis factor receptor family member rank mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Osteoblasts promote osteoclast differentiation through activation of nf. The mature osteoclasts were measured by bone resorption assays and trap staining. Quinn jm, elliott j, gillespie mt, martin tj 1998 a combination of osteoclast differentiation factor and macrophagecolony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro. Characterization of the osteoclastlineage cells in these mice provided important information on the stage of differentiation affected fig. In mice, treatment with agonists for tlr2, 4, and 5 results in osteoclast formation and extensive bone loss. Rankl, which is also known as the osteoclast differentiation factor, binds two types of receptors. Osteoclast differentiation an overview sciencedirect topics. Rap1 activation was maximal 15 min after rankl stimulation 63% of basal, p 0. Aspirin has been demonstrated to promote osteoblastmediated bone formation and inhibit osteoclast ocmediated bone resorption. The purpose of this study was to investigate the effect of zinc and determine its molecular mechanism on receptor activator of nf. A crucial role for reactive oxygen species in rankl. Transcriptional program of mouse osteoclast differentiation. Mmps expressed by the osteoclast include mmp9, 10, 12, and 14.
B ligand rankl is a key factor necessary for osteoclast differentiation and activation. The differentiation of osteoclasts, cells specialized for bone resorption, is governed by two key factors, macrophage colony stimulating factor mcsf and receptor activator of nuclear factor. It remains to be shown the relative importance of inhi. The molecular understanding of osteoclast differentiation. Signalling in osteoclasts and the role of fosap1 proteins. In this study, we investigated the effects of dehydrocostus lactone dl on osteoclast differentiation and activation and elucidated the possible mechanisms underlying these processes. It has been our experience that the in vitro cultivation of osteoclasts from bone marrow is largely dependent on seeding density. Request pdf osteoclast differentiation and activation osteoclasts are specialized cells derived from the monocytemacrophage haematopoietic lineage that. Osteoclasts initiate the process by resorbing discrete parts of old bone and later activate osteoblast differentiation and activation, migrate to the. Results 8cptcamp significantly increased osteoclast differentiation whereas bfa inhibited differentiation 13% p0. Nature volume 423, pages337342 2003 download citation. Mcsf is a key player in promoting the proliferation and survival of osteoclast precursor cells. During growth, the extension of the long bones is dependent on the function of chondrocyte proliferation in the growth plate 2, while the width increases as a result of bone accrual at the outer edge the periosteum along with bone erosion at the inner.
Depicted above this differentiation pathway is the potential role. Blimp1mediated repression of negative regulators is. Osteoclast differentiation an overview sciencedirect. Erk5 was activated by mcsf, which is one of the essential factors in osteoclast differentiation. As mentioned above, the naturally occurring and genetically modified osteopetrotic mice revealed a number of essential genes for osteoclast differentiation and activation. Aspirin inhibits ranklinduced osteoclast differentiation. Induction of osteoclast differentiation by runx2 through. Nov 25, 2010 in 1993, dr suda and his colleagues reported that the activated form of vitamin d, 1,25oh 2 vitamin d 3, induces bone marrow bm cells to locally produce c3, and that blocking c3 or c3 receptors using respective monoclonal antibodies mabs in bm cell cultures significantly inhibits 1,25oh 2 vitamin d 3 stimulated osteoclast oc differentiation.
May 15, 2003 osteoclasts are specialized cells derived from the monocytemacrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Many osteoclast precursor cell lines differentiate into osteoclasts in response to stimulation by mcsf and srankl 1,2. B ligand ranklinduced osteoclastogenesis in mouse bone marrowderived monocyte. Udagawa n, takahashi n, jimi e, matsuzaki k, tsurukai t, itoh k, et al. Activation of signaling pathways and induction of transcription factors required for osteoclastogenesis were investigated by realtime pcr and western blotting.
Radix paeoniae rubra stimulates osteoclast differentiation by. In 1993, dr suda and his colleagues reported that the activated form of vitamin d, 1,25oh 2 vitamin d 3, induces bone marrow bm cells to locally produce c3, and that blocking c3 or c3 receptors using respective monoclonal antibodies mabs in bm cell cultures significantly inhibits 1,25oh 2 vitamin d 3 stimulated osteoclast oc differentiation. Osteoblastsstromal cells also play an essential role in inducing osteoclast function osteoclast activation 4. Binding of rankl to rank results in the recruitment of cfos, and subsequent stimulation of cfos results in the activation of nfatc1 9, 10. Wess effectively inhibited osteoclast differentiation from its precursors. The mekerk pathways are critical for controlling cell proliferation and differentiation. The rank mrna was highly expressed by isolated bone marrowderived osteoclast progenitors and by mature osteoclasts. Selective regulation of mapk signaling mediates rankldependent osteoclast differentiation. A receptor that mediates osteoprotegerin ligand opglinduced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cdna library and is identical to the tumor necrosis factor receptor tnfr family member rank. To further elucidate the role of mir146a in osteoclast differentiation, the. Hyaluronan inhibits osteoclast differentiation via toll. Rip140 represses osteoclast differentiation and is degraded by rankl treatment in osteoclast differentiation. The understanding of osteoclasts oc differentiation and activation comes from the analysis of a family of biologically related tumor necrosis factor tnf and.
Bnuclear factor of activated t cell, cytoplasmic 1 nfatc1 signaling pathway. Two essential cytokines macrophage colonystimulating factor and the receptor activator of nuclear factor. The ligand for osteoprotegerin has been identified, and it is a tnfrelated cytokine that replaces the requirement for stromal cells, vitamin d3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. Ls was also observed to inhibit osteoclast differentiation and bone resorption. Previous work demonstrated that one mechanism by which bisphosphonates inhibit osteoclast differentiation and function is via inhibition of rap1a isoprenylation and, as a result, function.
The downstream activation of nf signaling was also inhibited by. Mesenchymal and hematopoietic lineages for the soil and seed, respectively, of osteoclast formation. It was the identification of rankl that lead to this, when it was recently identified as the major regulator of osteoclast formation, differentiation and survival 1618. Osteoprotegerin ligand is a cytokine that regulates. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by. We have detected the induction of rank, as reported previously fig.
Aspirin inhibits ranklinduced osteoclast differentiation in. Benzydamine inhibits osteoclast differentiation and bone resorption. The osteoclast differentiation factor osteoprotegerinligand. Mirna1224 is known for its role in nfkb activation and osteoclast differentiation of raw264. B ligandosteoclast differentiation factor expression in osteoblasts and inhibition of macrophage colony. The rank mrna was highly expressed by isolated bone marrowderived osteoclast progenitors and by mature. This is an attempt to give a birdseyeview of the players in osteoclast formation and differentiation in a brief and concise manner. N6methyladenosine m6a is an abundant mrna modification that has recently. Regulation of osteoclast differentiation by fibroblast. Addition of soluble rankl srankl also restored osteoclast differentiation in cocultures. A qrtpcr analyses of osteoclast markers in control flag or flagrip140overexpressing raw264. Oct 31, 2018 hsu hl, lacey dl, dunstan cr, solovyev i, colombero a, timms e et al 1999 tumor necrosis factor receptor family member rank mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Discovery of the rank signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption.
In both osteoclast precursor cells and mature osteoclasts, ranklrank signaling stimulates myc expression through asyet undefined mechanisms. The osteoclast differentiation factor osteoprotegerin. Mmp is believed to be involved in bone resorption and in osteoclast differentiation, as knockout mice revealed decreased osteoclast numbers, osteopetrosis, and decreased bone resorption. Zinc, an essential trace element, inhibits osteoclast differentiation in vitro and in vivo. Impact of cytokines and t lymphocytes upon osteoclast.
Request pdf osteoclast differentiation and activation in autoimmune arthritis, activation of t cells induces bone destruction through receptor activator of nfkappab ligand rankl. Activation of epac12 is essential for osteoclast formation. A crucial role for reactive oxygen species in ranklinduced. Studies on mice indicate that the molecular mechanism by which estrogen works appears to be the induction of osteoclast apoptosis by activation of. Rip140 in monocytesmacrophages regulates osteoclast. Bone erosion was evaluated after injection of mmpsilenced mdamb231 cells into nude mice femurs. Stimulating factor function in osteoclast precursors. Our functional assayed showed that tbi bone marrowderived evs activate nfkb signaling and osteoclast differentiation of bone marrow cells figure 5 and figure 7. Dl suppressed osteoclast differentiation by reducing the expression of the nuclear factor of.
Macrophage colonystimulating factor mcsf also is an essential cytokine for. In this study, we asked whether an arthritogenic organism could contribute to osteoclast differentiation and activation through regulation of the receptor activator of nf. Conditioned media from mdamb231 cells were added to peripheral blood mononuclear cultures to monitor pre osteoclast differentiation and activation. Actin ring structure of osteoclasts was detected fluorescently by staining for factin. Department of microbiology, laboratory of bone metabolism and control, yeungnam university college of medicine, daegu 705717, korea 2. View the article pdf and any associated supplements and figures for a period of 48 hours. According to our analysis 7, on the way to differentiating into adipocytes from. In the coculture system of osteoblasts and bone marrow cells, fgf. Mutations within the tnflike core domain of rankl have been recently reported in patients with osteoclastpoor autosomal recessive osteopetrosis. Regulation of osteoclast differentiation by fibroblast growth factor 2. Inhibition of mek5 by bix02189 or inhibition of erk5 by xmd 892 blocked osteoclast differentiation. Ba inhibits ranklinduced osteoclast differentiation and nfatc1 activation. The extracellular matrix ecm is an important factor influencing cell fate.
However, it remains unclear whether aspirin influences other immune cells during bone resorption. Water extract of spatholobus suberectus inhibits osteoclast. The molecular mechanism for the inhibitory effect of zinc, however, is poorly understood. Cyclic dinucleotides inhibit osteoclast differentiation.
The first one is rank, which is expressed in preosteoclasts. Erk5 activation is essential for osteoclast differentiation. Efficient osteoclast differentiation requires local. Kyunghee lee 1, yeoun ho chung 1, heejin ahn 1, hyunsoo kim 1, jaerang rho 2, daewon jeong 1. Cyclic dinucleotides inhibit osteoclast differentiation through sting. Ba inhibited osteoclast differentiation and strongly suppressed interleukin1. Tlr 2, 4, 5, and 9 are also expressed on osteoblasts and their activation increases osteoclast differentiation by an indirect mechanism through stimulation of rankl.
Zinc inhibits osteoclast differentiation by suppression of. Cells free fulltext bone marrow derived extracellular. The interaction between rank and rankl is essential for osteoclast differentiation and activation. Mmp stimulates osteoclast differentiation and activation in tumour breast bone metastases. Mutations within the tnflike core domain of rankl impair.