title: Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways.
abstract: The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate‑resistant acid phosphatase‑positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T‑score (r=‑0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC‑derived osteoclasts treated with curcumin were measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal‑regulated kinases 1 and 2, p38 and c‑Jun N‑terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c‑Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen‑activated protein kinase/RANK/c‑Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA.
authors: The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
authors: Wei
authors: W
authors: Shang
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Ling-Jie
authors: LJ
authors: Zhao
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Xiao-Lei
authors: XL
authors: Dong
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Zhi-Ming
authors: ZM
authors: Zhao
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Jing
authors: J
authors: Li
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Bei-Bei
authors: BB
authors: Zhang
authors: Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors: Hui
authors: H
authors: Cai
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050778:NFATC Transcription Factors / Q000276:immunology; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; D003474:Curcumin