Currently in the U.S., musculoskeletal conditions are the leading cause of disability. Joint diseases account for 50% of all chronic conditions in the elderly. Worldwide, OA is only the 6th leading cause of years of life lost to ill health. The burden of musculoskeletal disease, both in terms of human illness and heath care costs is projected to widen significantly by the year 2030. The aging of the U.S. population is expected to produce an additional 21 million individuals in the 65-and-over age group, representing a 20% increase over current demographics. Surprisingly, despite the wealth of clinical data on OA, surgical treatment which culminates in total joint replacement, remains the most effective therapy for progressive OA. Relatively little is known about the basic biology of OA especially how mechanical wear, the major hallmark of OA, influences fundamental biological control mechanisms in chondrocytes, the cells that populate cartilage.
Recently, through the use of specially-designed mechanical compression devices, we have found that chondrocytes respond to increasing mechanical loading signals much as other tissues respond to increasing concentrations of hormones or growth factors by activating 3 distinct MAPK signaling pathways, including the so-called ‘stress-activated’ protein kinase pathways. This finding not only opens the way for further research into what actions these signaling pathways have on specific genes involved in OA but also provides an opportunity to intervene with pathway-selective MAPK inhibitors in the treatment of OA.
The overall goal of Dr Fanning's projects is to advance the understanding of the molecular mechanisms of osteoarthritis (OA) progression through the novel finding that mechanical force activates critical cellular-signaling pathways in cartilage. Specific primary goals include:
- Mechanical Models of Arthritis