Piperine alleviates osteoclast formation through the p38/c-Fos/NFATc1 signaling axis.

Publisher: Ios Press Country of Publication: Netherlands NLM ID: 8807441 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8081 (Electronic) Linking ISSN: 09516433 NLM ISO Abbreviation: Biofactors Subsets: MEDLINE

Publication: Amsterdam : Ios Press
Original Publication: Oxford ; Washington, DC : Published for the International Union of Biochemistry by IRL Press, [c1988-

Alkaloids/*administration & dosage ; Benzodioxoles/*administration & dosage ; NFATC Transcription Factors/*biosynthesis ; Oncogene Proteins v-fos/*genetics ; Osteoporosis/*drug therapy ; Piperidines/*administration & dosage ; Polyunsaturated Alkamides/*administration & dosage ; p38 Mitogen-Activated Protein Kinases/*genetics; Animals ; Bone Resorption/drug therapy ; Bone Resorption/genetics ; Bone Resorption/pathology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Female ; Humans ; Mice ; NFATC Transcription Factors/genetics ; Oncogene Proteins v-fos/biosynthesis ; Osteoclasts/drug effects ; Osteoclasts/metabolism ; Osteoporosis/genetics ; Osteoporosis/pathology ; RANK Ligand/genetics ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases/biosynthesis

Increased bone fracture is one of the health risk factors in patients with bone loss related disorders such as osteoporosis and breast cancer metastasis to bone. Over activity of osteoclasts leads to uncoupling of bone remodeling favoring bone loss over bone formation. Receptor activator of nuclear factor-κβ ligand (RANKL) triggers the differentiation pathway leading to multinucleated osteoclast formation. Modulation of RANKL or its downstream signaling pathways involved in osteoclast formation is of significant interest in the development of anti-resorptive agents. In this study, the effects of piperine, an alkaloid present in Piper nigrum L. on osteoclast formation was investigated. Piperine inhibited tartrate-resistant acid phosphatase-positive multinucleated osteoclast formation in murine RAW264.7 macrophages and human CD14+ monocytes induced by RANKL and breast cancer cells. Piperine attenuated the p38-mitogen activated protein kinase pathway activation, while the extracellular-signal-regulated kinase, c-Jun N-terminal kinase, or NF-κβ pathways downstream of RANKL remained unaffected. Concomitantly, expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcription factors involved in osteoclastogenesis were remarkably inhibited by piperine. Furthermore, piperine disrupted the actin ring structure and bone resorption, a characteristic hallmark of osteoclasts. Collectively, these results suggested that piperine inhibited osteoclast differentiation by suppressing the p38/NFATc1/c-Fos signaling axis..
(© 2015 International Union of Biochemistry and Molecular Biology.)

Keywords: CD14+ monocytes; RANKL; RAW264.7; bone; breast cancer; osteoclast

0 (Alkaloids)
0 (Benzodioxoles)
0 (NFATC Transcription Factors)
0 (Oncogene Proteins v-fos)
0 (Piperidines)
0 (Polyunsaturated Alkamides)
0 (RANK Ligand)
0 (TNFSF11 protein, human)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
U71XL721QK (piperine)

Date Created: 20151203 Date Completed: 20161014 Latest Revision: 20211117

20240829

10.1002/biof.1241

26627060