title: Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model.
abstract: Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: F D
authors.initials: FD
authors.lastname: Tian
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: N
authors.initials: N
authors.lastname: An
authors.affiliation: Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: R H
authors.initials: RH
authors.lastname: Hao
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018771:Arthralgia / Q000188:drug therapy / Q000201:enzymology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D004195:Disease Models, Animal; D044950:Flavanones / Q000494:pharmacology*; D015870:Gene Expression; D053583:Interleukin-1beta / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D007719:Knee Joint / Q000201:enzymology* / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha / Q000032:analysis / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D053583:Interleukin-1beta; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D019278:Matrix Metalloproteinase 3; C005273:naringenin