scholarly journals Carbon Monoxide Inhibits Receptor Activator of NF-κB (RANKL)-Induced Osteoclastogenesis

2015 ◽  
Vol 36 (3) ◽  
pp. 1250-1258 ◽  
Author(s):  
Feng-Jen Tseng ◽  
Wei-Tso Chia ◽  
Chih-Hung Wang ◽  
Jia-Fwu Shyu ◽  
Guo-Hau Gou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Carbon Monoxide ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Rankl Expression ◽  
Arthritis Model ◽  
Ppar Γ ◽  
Pparγ Agonist ◽  
Receptor Activator

Background: Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-γB ligand (RANKL), one of the key stimulators of osteoclastogenesis. Methods: The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)-positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, Troglitazone. Results: CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells. Conclusions: CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-γ. Given the role of the PPAR-γ/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders.

Spatholobus suberectus Inhibits Osteoclastogenesis and Stimulates Chondrogenesis

2014 ◽  
Vol 42 (05) ◽  
pp. 1123-1138 ◽  
Author(s):  
Nam-Kyung Im ◽  
Sung-Gyu Lee ◽  
Dong-Sung Lee ◽  
Pil-Hoon Park ◽  
In-Seon Lee ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Chondral Defect ◽  
Active Components ◽  
Tnf Α ◽  
Receptor Activator ◽  
The Matrix ◽  
Spatholobus Suberectus

This study was carried out to investigate the effect of Spatholobus suberectus Dunn (SS) on the protection of chondral defect and inhibition of osteoclastogenesis. To examine these effects, we measured the matrix metalloproteinase (MMP) levels in SW1353 chondrosarcoma cells and performed tartrate-resistant acid phosphatase (TRAP) staining in bone marrow macrophage (BMM)-derived osteoclasts. To investigate the anti-osteoarthritis (OA) effects, we assessed TNF-α-induced MMP-1, -3, -9 and tissue inhibitors of matrix metalloproteinase (TIMP) expression levels in SW1353 cells. We observed that SS extract significantly inhibited MMP and TIMP expression in SW1353 cells. Also, SS extract inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. These results suggest that SS extract may have a potential in the treatment of bone loss and chondral defect by suppressing osteoclast differentiation and decreasing the expression of OA factors. Therefore, clarification of the mechanism of the action of SS extract and its active components is needed.

Amelogenin-mediated Regulation of Osteoclastogenesis, and Periodontal Cell Proliferation and Migration

2006 ◽  
Vol 85 (2) ◽  
pp. 144-149 ◽  
Author(s):  
J. Hatakeyama ◽  
D. Philp ◽  
Y. Hatakeyama ◽  
N. Haruyama ◽  
L. Shum ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Periodontal Ligament ◽  
Periodontal Ligament Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Wild Type ◽  
Rankl Expression ◽  
Migration Rates ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

We previously reported that amelogenin isoforms M180 and leucine-rich amelogenin peptide (LRAP) are expressed in the periodontal region, and that their absence is associated with increased cementum defects in amelogenin-knockout (KO) mice. The aim of the present study was to characterize the functions of these isoforms in osteoclastogenesis and in the proliferation and migration of cementoblast/periodontal ligament cells. The co-cultures of wild-type (WT) osteoclast progenitor and KO cementoblast/periodontal ligament cells displayed more tartrate-resistant acid phosphatase (TRAP)-positive cells than the co-cultures of WT cells. The addition of LRAP to both co-cultures significantly reduced RANKL expression and the TRAP-positive cells. Proliferation and migration rates of the KO cementoblast/periodontal ligament cells were lower than those of WT cells and increased with the addition of either LRAP or P172 (a porcine homolog of mouse M180). Thus, we demonstrate the regulation of osteoclastogenesis by LRAP, and the proliferation and migration of cementoblast/periodontal ligament cells by LRAP and P172.

scholarly journals Anti-Müllerian Hormone Negatively Regulates Osteoclast Differentiation by Suppressing the Receptor Activator of Nuclear Factor-κB Ligand Pathway

2021 ◽  
Vol 28 (3) ◽  
pp. 223-230
Author(s):  
Jung Ha Kim ◽  
Yong Ryoul Yang ◽  
Ki-Sun Kwon ◽  
Nacksung Kim
Keyword(s):  
Osteoblast Differentiation ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Bone Morphogenetic Protein 2 ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Alizarin Red ◽  
Receptor Activator

Background: Multiple members of the transforming growth factor-β (TGF-β) superfamily have well-established roles in bone homeostasis. Anti-Müllerian hormone (AMH) is a member of TGF-β superfamily of glycoproteins that is responsible for the regression of fetal Müllerian ducts and the transcription inhibition of gonadal steroidogenic enzymes. However, the involvement of AMH in bone remodeling is unknown. Therefore, we investigated whether AMH has an effect on bone cells as other TGF-β superfamily members do.Methods: To identify the roles of AMH in bone cells, we administered AMH during osteoblast and osteoclast differentiation, cultured the cells, and then stained the cultured cells with Alizarin red and tartrate-resistant acid phosphatase, respectively. We analyzed the expression of osteoblast- or osteoclast-related genes using real-time polymerase chain reaction and western blot.Results: AMH does not affect bone morphogenetic protein 2-mediated osteoblast differentiation but inhibits receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation. The inhibitory effect of AMH on osteoclast differentiation is mediated by IκB-NF-κB signaling.Conclusions: AMH negatively regulates osteoclast differentiation without affecting osteoblast differentiation.

scholarly journals Interleukin (IL)-25 suppresses IL-22 induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

2020 ◽  
Author(s):  
Hong Ki Min ◽  
Ji-Yeon Won ◽  
Bo-Mi Kim ◽  
Kyung-Ann Lee ◽  
Seoung-Joon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
P38 Mapk ◽  
Human Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Blood Monocytes ◽  
Rankl Expression

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, as well as synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were up-regulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

scholarly journals Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis

2019 ◽  
Vol 20 (6) ◽  
pp. 1467 ◽  
Author(s):  
Hyung Joon Kim ◽  
Ha Jin Kim ◽  
YunJeong Choi ◽  
Moon-Kyoung Bae ◽  
Dae Seok Hwang ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Clinical Importance ◽  
Osteonecrosis Of The Jaw ◽  
Severe Side Effect ◽  
Signal Transducer ◽  
Rankl Expression ◽  
Receptor Activator ◽  
Subsequent Activation ◽  
Transcription 3 ◽  
Nuclear Factor Kb

Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.

scholarly journals Modulatory Effect of 1,25-Dihydroxyvitamin D3on IL1β-Induced RANKL, OPG, TNFα, and IL-6 Expression in Human Rheumatoid Synoviocyte MH7A

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoke Feng ◽  
Chengyin Lv ◽  
Fang Wang ◽  
Ke Gan ◽  
Miaojia Zhang ◽  
...  
Keyword(s):  
Biological Function ◽  
Bone Erosion ◽  
Osteoclast Formation ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Potent Inducer ◽  
Receptor Activator ◽  
Inflammatory Milieu ◽  
Vitamin D Supplement ◽  
Inflammatory Action

Receptor activator of nuclear factorκB ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)2D3has been suggested as a potent inducer of RANKL expression, it should clarify whether vitamin D supplement could result in RANKL overexpression and thereby facilitate excessive osteoclastogenesis and bone resorption in RA. Here, we investigated modulatory effect of 1,25(OH)2D3on the expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were stimulated with IL1βand then treated with different concentrations of 1,25(OH)2D3for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNFβmRNA expression in cells and IL-6 protein in supernatants were observed in IL1β-induced MH7A in the presence of 1,25(OH)2D3compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3and IL1β. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)2D3could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteoclastogenesis in RA.

The Inhibitory Effect of Angelica tenuissima Water Extract on Receptor Activator of Nuclear Factor-Kappa-B Ligand-Induced Osteoclast Differentiation and Bone Resorbing Activity of Mature Osteoclasts

2015 ◽  
Vol 43 (04) ◽  
pp. 715-729 ◽  
Author(s):  
Sung-Jun Ahn ◽  
Jong Min Baek ◽  
Yoon-Hee Cheon ◽  
Sun-Hyang Park ◽  
Myeung Su Lee ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Water Extract ◽  
Tartrate Resistant Acid Phosphatase ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Metabolic Bone Disorder ◽  
Receptor Activator

Angelica tenuissima has been traditionally used in oriental medicine for its therapeutic effects in headache, toothache, and flu symptoms. It also exerts anti-inflammatory activity via the inhibition of the expression of cyclooxygenase-2 (COX-2). However, the effect of Angelica tenuissima on osteoclast differentiation has not been identified until recently. In this study, we first confirmed that Angelica tenuissima water extract (ATWE) significantly interrupted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) in a dose-dependent manner without any cytotoxicity. Next, we clarified the underlying mechanisms linking the suppression effects of ATWE on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. At the molecular level, ATWE induced the dephosphorylation of c-Jun N-terminal kinase (JNK) and Akt and decreased the degradation of IκB in RANKL-dependent early signaling pathways. Subsequently, ATWE caused impaired activation of the protein and mRNA levels of c-Fos and nuclear factor of activated T cell c1 (NFATc1). Moreover, the disassembly of filamentous actin (F-actin) ring and anti-resorptive activity of mature osteoclasts were triggered by ATWE treatment. Although ATWE did not enhance osteogenesis in primary osteoblasts, our results showed that ATWE is a potential candidate for anti-resorptive agent in osteoporosis, a common metabolic bone disorder.

scholarly journals Calcitonin inhibits osteoclast formation in mouse haematopoetic cells independently of transcriptional regulation by receptor activator of NF-κB and c-Fms

2007 ◽  
Vol 195 (3) ◽  
pp. 415-427 ◽  
Author(s):  
Susanne Granholm ◽  
Pernilla Lundberg ◽  
Ulf H Lerner
Keyword(s):  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Osteoclast Progenitor ◽  
Receptor Activator ◽  
Macrophage Colony ◽  
A Disintegrin And Metalloproteinase

The effects of calcitonin (CT) on osteoclast formation and gene expression have been studied in cultured mouse spleen cells and mouse bone marrow macrophages (BMMs). CT inhibited the formation of multinucleated osteoclasts and resorption pits in spleen cell cultures and BMM as well as in CD115+ CD3− CD45R−sorted BMM cultures, incubated in the presence of macrophage colony-stimulating factor and receptor activator of NF-κB ligand (RANKL). No effect on apoptosis by CT was observed. CT did not affect the mRNA expressions of RANK and c-Fms, or the mRNA expressions of a wide variety of transcription factors and genes important for osteoclast differentiation and activity. CT induced inhibition of tartrate-resistant acid phosphatase (TRAP), positive multinucleated osteoclast formation was not associated with any decrease of total TRAP activity, resulting in a large number of TRAP+ mononucleated cells in CT-treated cultures. CT did not affect the mRNA expression of dendritic cell-specific transmembrane protein, d2 isoform of vacuolar (H+) ATPase vo domain, a disintegrin and metalloproteinase domain 8 (ADAM8), ADAM12, DNAX-activating protein or Fc receptor common γ chain suggested to be involved in fusion of mononucleated osteoclast progenitor cells. The inhibitory effect by CT was mimicked not only by compounds activating cAMP and protein kinase A (PKA) but also by a cAMP analogue activating the exchange protein directly activated by cAMP (Epac) pathway. It is concluded that CT, through cAMP/PKA/Epac cascades, inhibits osteoclast formation and that this effect is not associated with decreased transcription of genes known to be important for osteoclast progenitor cell differentiation, fusion or function.

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