Research Issue - Harvard School of Dental Medicine

harvarddentalbulletinWinter 2010–11Volume 70Number 3Research FocusHSDM Research Targets OsteoarthritisStudies by Yefu Li and Dorothy Pazin hold promise for therapy and prevention.Osteoarthritis (OA) represents an enormous socioeconomicburden. Persons with the disease suffer from chronic the possibility of using this extracellular part of DDR2 as a“This very encouraging information prompts us to think aboutpain that greatly reduces quality of life and costs the economy therapeutic agent for the treatment of OA,” says Li. “We planmore than $125 billion per year in lost working days and medicaland surgical costs. The complicated causes of the disease OA progression in a mouse model of OA.” If successful, says Li,to test whether the extracellular part of the receptor can delayand largely unknown mechanisms by which OA ensues make this research will confirm the DDR2-collagen interaction as ait very difficult to identify effective therapeutic targets for novel target for OA therapy and serve as a prelude to evaluatingtreatment. Recently, several drugs usedfor the treatment of arthritic pain havebeen found to have severe side effects,and some, such as Vioxx, have beenwithdrawn. Therefore, new therapeuticagents for the treatment of osteoarthritisare urgently needed, and researchersat HSDM are pursuing promising pathstoward this end.treatmentOne of those researchers is Yefu Li, an HSDM assistant professorof developmental biology. Although the initial events of OAare diverse, he notes, the pathologic progression of the diseasefollows a consistent pattern (articular cartilage degeneration).Thus, an understanding of the molecular pathway underlyingthis pathologic progression is critical in treating this disease.In the past few years, Li and colleagues have been using mouseOA models and human OA cartilages to investigate molecularmechanisms responsible for the articular cartilage degeneration.The team discovered the existence of a novel pathwaymediated by activation of a cell membrane receptor for type IIcollagen (DDR2) that leads to the irreversible loss of cartilagein mouse models of OA. Since activation of DDR2 requiresbinding of the receptor to type II collagen, blocking interactionof DDR2 with the type II collagen can inhibit activationof DDR2. This strongly suggests that agents that interrupt theinteraction of the DDR2 with type II collagen can inhibit thispathway.The complicated causes ofosteoarthritis and the largelyunknown mechanisms by whichit ensues make it very difficultto identify effective therapeutictargets for treatment.the extracellular part of the DDR2 asa possible therapeutic for human OA.preventionDorothy Pazin, a 2010–2011 HSDMDean’s Scholar, is pursuing a pathtoward OA prevention through aninvestigation of the developmentalorigins of the meniscus. A fibrocartilaginousdisc in the knee, the meniscusprotects the joint from damage by distributing weight andabsorbing shock that occurs during normal knee movement.Damage to the meniscus by sports injury, traumatic accident,and normal wear and tear is common and is a predictorof future development of osteoarthritis. Efforts to repair themeniscus are largely unsuccessful because of the poor healingability of the tissue and the lack of effective treatment strategies.“Normal tissue repairs itself, but the meniscus has avery limited capacity for repair and regeneration,” says Pazin,a postdoctoral fellow in the laboratory of Vicki Rosen, headof the Department of Developmental Biology. Given that thesequence of events that occurs during repair of other musculoskeletaltissues often recapitulates developmental processes, theresearchers hypothesize that the regulatory molecules that controlmeniscal morphogenesis may be effective meniscal repairagents. Pazin and her team expect that their work will lead to agreater understanding of the embryonic origins of the meniscusand the genes and signaling pathways that control its development.These answers will lead to potential therapeutics formeniscal injury and to preventive strategies for osteoarthritis.H10