title: Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.
abstract: Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future.
authors: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois 60612, USA.
authors: Dongyao
authors: D
authors: Yan
authors: Di
authors: D
authors: Chen
authors: Jie
authors: J
authors: Shen
authors: Guozhi
authors: G
authors: Xiao
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Hee-Jeong
authors: HJ
authors: Im
mesh_terms: D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D010450:Endopeptidases / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D007781:Lactoferrin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008875:Middle Aged; D013583:Synovial Membrane / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C508585:IL1B protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016222:Fibroblast Growth Factor 2; C082171:lactoferricin B; D010450:Endopeptidases; D007781:Lactoferrin; D020782:Matrix Metalloproteinases; C083641:aggrecanase