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Paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38 and NF-kappaB pathway.
Eur J Pharmacol. 2008 Jun 24; 588(1):124-33.EJ

Abstract

Numerous studies have indicated that inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory activity. Here we found that paeonol markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. In addition, in an assay of osteoclast activity on substrate plates, paeonol significantly decreased the resorption activity of mature osteoclasts. Treatment of RAW264.7 macrophages with RANKL induced extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation. However, RANKL-induced ERK, p38 but not JNK phosphorylation was attenuated by paeonol. Furthermore, RANKL-mediated increase of IkappaBalpha phosphorylation, p65 phosphorylation at Ser(536), kappaB-luciferase activity and NF-kappaB binding activity was inhibited by paeonol. In addition, paeonol also prevented the bone loss inducing by ovariectomy in vivo. Our data suggest that paeonol inhibits osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuated of RANKL-induced ERK, p38 and NF-kappaB activation, which in turn protect bone loss from ovariectomy.

Authors+Show Affiliations

School of Pharmacy, China Medical University, Taichung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18495114

Citation

Tsai, Huei-Yann, et al. "Paeonol Inhibits RANKL-induced Osteoclastogenesis By Inhibiting ERK, P38 and NF-kappaB Pathway." European Journal of Pharmacology, vol. 588, no. 1, 2008, pp. 124-33.
Tsai HY, Lin HY, Fong YC, et al. Paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38 and NF-kappaB pathway. Eur J Pharmacol. 2008;588(1):124-33.
Tsai, H. Y., Lin, H. Y., Fong, Y. C., Wu, J. B., Chen, Y. F., Tsuzuki, M., & Tang, C. H. (2008). Paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38 and NF-kappaB pathway. European Journal of Pharmacology, 588(1), 124-33. https://doi.org/10.1016/j.ejphar.2008.04.024
Tsai HY, et al. Paeonol Inhibits RANKL-induced Osteoclastogenesis By Inhibiting ERK, P38 and NF-kappaB Pathway. Eur J Pharmacol. 2008 Jun 24;588(1):124-33. PubMed PMID: 18495114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38 and NF-kappaB pathway. AU - Tsai,Huei-Yann, AU - Lin,Hui-Yi, AU - Fong,Yi-Chin, AU - Wu,Jin-Bin, AU - Chen,Yuh-Fung, AU - Tsuzuki,Minoru, AU - Tang,Chih-Hsin, Y1 - 2008/04/16/ PY - 2007/12/16/received PY - 2008/03/23/revised PY - 2008/04/02/accepted PY - 2008/5/23/pubmed PY - 2008/8/23/medline PY - 2008/5/23/entrez SP - 124 EP - 33 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 588 IS - 1 N2 - Numerous studies have indicated that inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory activity. Here we found that paeonol markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. In addition, in an assay of osteoclast activity on substrate plates, paeonol significantly decreased the resorption activity of mature osteoclasts. Treatment of RAW264.7 macrophages with RANKL induced extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation. However, RANKL-induced ERK, p38 but not JNK phosphorylation was attenuated by paeonol. Furthermore, RANKL-mediated increase of IkappaBalpha phosphorylation, p65 phosphorylation at Ser(536), kappaB-luciferase activity and NF-kappaB binding activity was inhibited by paeonol. In addition, paeonol also prevented the bone loss inducing by ovariectomy in vivo. Our data suggest that paeonol inhibits osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuated of RANKL-induced ERK, p38 and NF-kappaB activation, which in turn protect bone loss from ovariectomy. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18495114/Paeonol_inhibits_RANKL_induced_osteoclastogenesis_by_inhibiting_ERK_p38_and_NF_kappaB_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00442-1 DB - PRIME DP - Unbound Medicine ER -