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Gene. 2013 Sep 25;527(2):440-7. doi: 10.1016/j.gene.2013.05.069. Epub 2013 Jul 2.

A current review of molecular mechanisms regarding osteoarthritis and pain.

Author information

1
Department of Biochemistry, Rush University Medical Center, University of Illinois, Chicago, IL 60612, USA.

Abstract

Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.

KEYWORDS:

ADAMTS-4; Anti-IL-1; BMP-7; Biochemical mediators; COX; Cartilage; DRG; E prostanoid receptor; ECM; EP; ERK; FGF-2; FGFR1-Ras; Fn-f; IGF-1; IL; IL-1ra; IL-1β; IVD; JNK; LIF; Lf; LfcinB; MAPKs; MMP; NFκB; NSAIDS; OA; Osteoarthritic pain; Osteoarthritis; PG; PGD2; PGE synthase; PGE2; PGES; PGF2Fa; PGI2; PKCδ; RA; RNA; ROS; RSV; SP; TNF-α; TNFR; a disintergrin and metalloproteinase with thrombospondin motifs; anti-interleukin 1; bone morphogenetic protein 7; bovine lactoferrin; c-Jun N-terminal kinase; cAMP; cyclic adenosine monophosphate; cyclooxygenase; dorsal root ganglion; extracellular matrix; extracellular signal-regulated kinase; fibroblast growth factor 2; fibroblast growth factor receptor 1-Ras; fibronectin fragment; iNOS; inducible nitric oxide synthase; insulin-like growth factor 1; interleukin; interleukin-1 beta; interleukin-1 receptor antagonist; intervertebral disk; lactoferrin; leukemia inducing factor; mPGES-1; mRNA; matrix metalloproteinase; messenger ribonucleic acid; microsomal prostaglandin E synthase-1; mitogen-activated protein kinase; nonsteroidal anti-inflammatory drugs; nuclear factor kappa-light-chain-enhancer of activated B cells; osteoarthritis; prostaglandin D2; prostaglandin E2; prostaglandin I2; prostaglandin fibroblast growth factor alpha; protein kinase C alpha; proteoglycan; reactive oxygen species; resveratrol; rheumatoid arthritis; ribonucleic acid; substance P; tumor necrosis factor alpha; tumor necrosis factor receptor

PMID:
23830938
PMCID:
PMC3745800
DOI:
10.1016/j.gene.2013.05.069
[Indexed for MEDLINE]
Free PMC Article

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