Amorphigenin inhibits Osteoclast differentiation by suppressing c-Fos and nuclear factor of activated T cells

Kim, Bong Gyu; Kwak, Han Bok; Choi, Eun Ae; Kim, Hun Soo; Kim, Myung Hee; Kim, Seong Hwan; Choi, Mi‐Jin; Chun, Churl Hong; Oh, Jae‐Min; Kim, Jeong-Joong

doi:10.5115/acb.2010.43.4.310

Cited by 8 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of osteoclasts plays a key role in destructive bone diseases. To further explore the potential protective effects of AP under pathological conditions, we used LPS‐induced osteolysis in mice to model inflammatory osteolysis (Kim et al ., ; Kwak et al ., ; Lee et al ., ; Khor et al ., ; Zhang et al ., ). Mice were intraperitoneally injected with LPS with or without AP.…”

Section: Resultsmentioning

confidence: 99%

Andrographolide suppresses RANKL‐induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

Zhai

Liu

et al. 2014

British J Pharmacology

102

View full text Add to dashboard Cite

Background and Purpose Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast‐related diseases. Here, we examined changes in osteoclastogenesis and LPS‐induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. Experimental Approach Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT‐PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. Key Results AP concentration‐dependently suppressed RANKL‐mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast‐specific markers, including tartrate‐resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL‐induced NF‐κB signalling by inhibiting the phosphorylation of TGF‐β‐activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF‐κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. Conclusions and Implications AP suppressed RANKL‐induced osteoclastogenesis through attenuating NF‐κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast‐related bone diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Andrographolide suppresses RANKL‐induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

Zhai

Liu

et al. 2014

British J Pharmacology

102

View full text Add to dashboard Cite

show abstract

“…Osteoclasts are bone-resorbing multinuclear cells, which originate from hematopoietic stem cells of the monocyte/macrophage lineage (6). The differentiation of osteoclasts is regulated by the two cytokines, receptor activator of nuclear factor (NF) κ-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) (7).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract

Choi

Park

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Osteoclasts, derived from hematopoietic stem cells, are specialized macrophages and have a homeostatic role in skeletal modeling and remodeling with bone-forming osteoblasts. However, excessive osteoclast activity induces bone diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Natural substances have received attention as therapeutic drugs in human diseases. In the current study, cells isolated from mouse bone marrow, and a mouse model, were used to determine the effect of centipedegrass extract (CGE) on osteoclasts. Multiple concentrations of CGE were administered to bone marrow cells for 24‑72 hours and, for the in vivo study, mice were treated with CGE for 8 days. The effects of CGE on transcription and translation of osteoclast-associated molecules were then determined using reverse transcription-polymerase chain reaction and immunoblotting, respectively. In the present study it was shown that CGE extracted from Eremochloa ophiuroides (centipedegrass) inhibited receptor activator of nuclear factor κ‑B ligand (RANKL)‑mediated osteoclast differentiation in bone marrow macrophages, without cytotoxicity, in a dose‑dependent manner. CGE decreased the expression levels of osteoclast‑specific genes, including matrix metalloproteinase‑9, osteoclast‑associated immunoglobulin‑like receptor and cathepsin K, however, CGE had no inhibitory effect on the expression levels of mitogen‑activated protein kinases, nuclear factor‑κB and Akt. Furthermore, the protein and RNA levels of RANKL‑induced c‑Fos and nuclear factor of activated T-cell cytoplasmic 1 were suppressed by CGE. These results indicated that CGE may serve as a useful drug in the prevention of bone loss.

show abstract

“…The amount of negative regulators of bone resorption in assays in vitro may be less than that in assays in vivo. This discrepancy may be dependent on the assay conditions (Kim et al, ; Kwak et al, ; Kim et al, ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of RANKL‐dependent cellular fusion in pre‐osteoclasts by amiloride and a NHE10‐specific monoclonal antibody

Mine

Shuto

Nikawa

et al. 2015

Cell Biology International

View full text Add to dashboard Cite

The functions of Na(+) /H(+) exchangers (NHEs) during osteoclastic differentiation were investigated using the NHE inhibitor amiloride and a monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells, amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with ≥10 nuclei and increased the number of small TRAP-positive OCs with ≤10 nuclei during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10 mRNA expression and OC differentiation markers were increased by sRANKL stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the number of small TRAP-positive OCs. These findings suggested that inhibition of NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion. The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone resorption for targeted bone disease therapy.

show abstract

Amorphigenin inhibits Osteoclast differentiation by suppressing c-Fos and nuclear factor of activated T cells

Cited by 8 publications

References 27 publications

Andrographolide suppresses RANKL‐induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

Andrographolide suppresses RANKL‐induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo

Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract

Inhibition of RANKL‐dependent cellular fusion in pre‐osteoclasts by amiloride and a NHE10‐specific monoclonal antibody

Contact Info

Product

Resources

About