REGENERATIVE THERAPYFOR OSTEOARTHRITIS

摘要

Osteoarthritis (OA) is a common cause of lameness, pain, and dysfunction in dogs and is estimated to affect more than 20% of all dogs over 1 year old (Zachos and Berton 2005). It most often occurs secondary to a variety of conditions, including jointlaxity, instability or incongruity, osteochondrosis, trauma, or infection. Regardless of the initiating cause, the end results are the same: altered metabolism and degradation of articular cartilage, changes to the subchrondral and periarticular bone, synovial inflammation, and fibrosis. Cross talk, mediated by cytokines, between joint tissues (cartilage and synovium, in particular) is thought to play a central role in the initiation and progression of these changes. Cartilage breakdown products, resulting from mechanical or enzymatic destruction, induce the release of inflammatory cytokines (e.g., IL-1, IL-6, TNF-a) by macrophages and chondrocytes, leading to the upregulation of matrix metalloproteinases (MMPs), nitric oxide (NO), and other proteolytic enzymes. At the same time, there is a decrease in the production of the inhibitors of these enzymes and impairment in the repair response (decreased TGF-p, IGF-1/2 binding), ultimately leading to further extracellular matrix (ECM) degradation and celldeath. Synovitis is a common feature in dogs (unlike people), and the synovium appears to be a major contributor to pain associated with osteoarthritis. Our understanding of pain associated with osteoarthritis is generally poor. Joint pain is often described as dull or aching and is poorly localized. The structures of the joint, with the exception of articular cartilage, are innervated primarily by large C-fibers. These fibers, silent in normal joints, respond to mechanical stimulation of the inflamed joint. This sensitization is the result of the effects of inflammatory mediators (IL-6, TNF-a, prostaglandins, substance P, etc.).