Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway

Choi, Jiwon; Choi, So Yoon; Lee, Sun Young; Lee, Jae Yoon; Kim, Hong Sung; Lee, Soo Young; Lee, Na Kyung

doi:10.1016/j.cellsig.2013.02.015

Cited by 51 publications

(41 citation statements)

References 27 publications

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“…We used p38 MAPK inhibitor as a positive control for RANKL-induced osteoclastogenesis in vitro , given the evidence that attenuation of phosphorylation status of p38 leads to the inhibition of transcription factor, NFATc1 at the protein level (Pivetta et al, 2011; Choi et al, 2013). We observed the compound of p38 strongly inhibited osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption

et al. 2019

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Osteoclasts are responsible for bone erosion in osteoporosis and rheumatoid arthritis (RA). Both Btk and Tec kinases have essential functions in osteoclast differentiation. Tirabrutinib is a highly potent and dual oral Btk/Tec inhibitor with an IC50 in the nmol/L range and significantly inhibits the M-CSF and RANKL-driven osteoclast differentiation. It was hypothesized that the in vitro activity of tirabrutinib could be demonstrated in mice bone resorption model. The RANKL model studies show that tirabrutinib significantly suppressed bone loss with the inhibition of serum TRAPCP5b and urinary CTX-1. Bone Mineral Density (BMD) loss in tirabrutinib-treated mice was 55% (P < .05), 87% (P < .001) and 88% (P < .001) for the 3, 10 and 30 mg/kg dose groups respectively.Btk and Tec are required for osteoclast differentiation and activation based on the genetic evidence obtained from Btk and Tec double deficient mice. Tirabrutinib may be a novel therapeutic target for bone diseases, such as osteoporosis and RA.

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Section: Discussionmentioning

confidence: 99%

Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption

et al. 2019

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“…This result is somewhat enigmatic, as the expression of both DC-STAMP and ATP6v0d2 is regulated by the same transcription factor NFATc1. 21,22) However, it is possible that ISG15 affects the factor(s) responsible for the regulation of ATP6v0d2 expression.…”

Section: Isg15 Suppresses Atp6v0d2mentioning

confidence: 99%

ISG15 Regulates RANKL-Induced Osteoclastogenic Differentiation of RAW264 Cells

Takeuchi

Shimakawa

Tamura

et al. 2015

Biological & Pharmaceutical Bulletin

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Interferon-stimulated gene 15 kDa (ISG15) is a protein upregulated by interferon-β that negatively regulates osteoclastogenesis. We investigated the role of ISG15 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells. RANKL stimulation induced ISG15 expression in RAW264 cells at both the mRNA and protein levels. Overexpression of ISG15 in RAW264 cells resulted in suppression of cell fusion in RANKL-stimulated cells as well as the reduced expression of ATP6v0d2, a gene essential for cell fusion in osteoclastogenic differentiation. These results suggest that ISG15 suppresses RANKL-induced osteoclastogenesis, at least in part, through inhibition of ATP6v0d2 expression.Key words interferon-stimulated gene 15 kDa (ISG15); osteoclast; interferon; receptor activator of nuclear factor-κB ligand (RANKL); RAW264; ATP6v0d2Interferon-α/β is a multifunctional cytokine that exerts various biological functions in immunity, cell differentiation, and so on via the induction of downstream genes called interferonstimulated genes (ISGs).1,2) Interferon-stimulated gene 15 kDa (ISG15), a ubiquitin-like protein, is one of the proteins that are most upregulated by interferon stimulation.3,4) Upon stimulation of the cells with interferon or pathogenic materials such as lipopolysaccharides, the expression of ISG15 and several other enzymes that catalyze protein modification with ISG15 (ISGylation) is induced, followed by the ISGylation of various cellular proteins. ISGylation affects the nuclear factor-kappa B (NF-κB) signaling pathway as well as the activity of doublestranded RNA-activated protein kinase, 5,6) both of which have important roles in osteoclastogenic differentiation. 7,8) Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells derived from monocyte/macrophage lineage cells. 7,9) Receptor activator of nuclear factor-κB ligand (RANKL) is essential for the induction of osteoclastogenesis.10) The murine RAW264 cell line is a useful model of osteoclastogenesis as, upon stimulation with RANKL, RAW264 cells differentiate into TRAP-positive mononuclear cells, which subsequently undergo cell fusion to form TRAPpositive multinuclear osteoclasts. In vivo, osteoclastogenesis is tightly controlled by factors produced from cells such as osteoblasts and osteocytes, and deregulation of osteoclastogenesis results in various diseases such as osteoporosis. 7,9,11,12)

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“…Among which DC‐STAMP has been studied quite intensively about its regulating mechanism (Courtial et al, ; Zhu et al, ). Chemical compound like caffeine, vitamin E, and Gymnasterkoreayne F have been reported regulating osteoclastogenesis by modulating DC‐STAMP (Kim et al, ; Fujita et al, ; Choi et al, ). In our study, we also reported that cyanidin regulates OCPs fusion by targeting DC‐STAMP, OC‐STAMP, CD9, and ATP6v0d2.…”

Section: Discussionmentioning

confidence: 99%

Dual Effect of Cyanidin on RANKL‐Induced Differentiation and Fusion of Osteoclasts

Dou

Kang

et al. 2015

Journal Cellular Physiology

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Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells derived from hematopoietic stem cells (HSCs) or monocyte/macrophage progenitor cells and formed by osteoclasts precursors (OCPs) fusion. Cyanidin is an anthocyanin widely distributed in food diet with novel antioxidant activity. However, the effect of cyanidin on osteoclasts is still unknown. We investigated the effect of cyanidin on RANKL-induced osteoclasts differentiation and cell fusion. The results showed that cyanidin had a dual effect on RANKL-induced osteoclastogenesis. Lower dosage of cyanidin (< 1 µg/ml) has a promoting effect on osteoclastogenesis while higher dosage of cyanidin (> 10 µg/ml) has an inhibitory effect. Fusogenic genes like CD9, ATP6v0d2, DC-STAMP, OC-STAMP, and osteoclasts related genes like NFATc1, mitf, and c-fos were all regulated by cyanidin consistent to its dual effect. Further exploration showed that low concentration of cyanidin could increase osteoclasts fusion whereas higher dosage of cyanidin lead to the increase of LXR-β expression and activation which is suppressive to osteoclasts differentiaton. All these results showed that cyanidin exhibits therapeutic potential in prevention of osteoclasts related bone disorders.

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Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway

Cited by 51 publications

References 27 publications

Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption

Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption

ISG15 Regulates RANKL-Induced Osteoclastogenic Differentiation of RAW264 Cells

Dual Effect of Cyanidin on RANKL‐Induced Differentiation and Fusion of Osteoclasts

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