What is osteoarthritis… and can stem cells help?

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What is osteoarthritis… and can stem cells help?



Articular cartilage is the gristle that caps the ends of long bones. It consists primarily of a matrix of proteoglycans which are complex arrangements of proteins and glycogen molecules. The proteoglycans exist within a framework of tough collagen fibers. Within the proteoglycan matrix are cells called chondrocytes. These cells are the ones that are responsible for the synthesis of proteoglycans. In fact, the normal maintenance of cartilage integrity is highly dependent on the normal metabolic function of these chondrocytes.
Healthy cartilage can withstand the usual loads that accompany the activities of daily living. Cartilage, when loaded, acts as a shock absorber. It will partially deform but springs back to its normal shape under normal circumstances. It also provides a gliding surface which is enhanced by a small amount of synovial fluid, produced by the joint lining, that acts as a lubricant.
Osteoarthritis is a degenerative disease of articular cartilage. It arises as a result of the inability of cartilage to keep up with excessive breakdown. The first step is a disturbance in the matrix. This causes loss of cartilage resiliency. In addition, proteins that promote inflammation (called inflammatory cytokines) are produced by the joint lining. These cytokines activate destructive enzymes, called proteases. The proteases degrade the matrix and cause the chondrocyte to malfunction.
The inflammatory cytokines cause the production of other bad chemicals including nitric oxide and matrix metalloproteinases. These cause further cartilage breakdown.
Over time, cartilage wears away, underlying bone is exposed, and joint deformity occurs. Pain and disability are the end result.
The knee is a particular target of osteoarthritis.
With the aging demographic as well as the increasing incidence of obesity, knee osteoarthritis (KOA) is a significant public health problem. Significant disability can result and health care dollars are being spent at an astonishing rate for total knee replacement. The 2003 National Institutes of Health Consensus Statement on Total Knee Replacement estimated that the mean total cost of a knee replacement in the United States was $35,000. That figure is obviously higher now. And the dollar cost does not factor in the potential for complications.
More than half a million knee replacements occur annually and that figure will continue to rise.
Non-surgical treatments by and large are palliative. These include education, weight loss, analgesics, non-steroidal anti-inflammatory drugs (NSAIDS), braces, physical therapy, exercise, and injections of glucocorticoids and viscosupplements (lubricants).
Investigational therapies aimed at either increasing the production of matrix and/or collagen or reducing the amount of inflammatory cytokines are being scrutinized but so far, there is little cause for optimism.
More recently, the use of autologous stem cells, have been shown to have promise for KOA (Wei N, et al. Guided mesenchymal layering technique for treatment of osteoarthritis of the knee. J Applied Research. 2011; 11)
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