Apoptosis in Articular Cartilage After Injury is Dependent on Estrogen Status in Experimental Osteoarthritis

Introduction: Epidemiological studies have shown that there are significant gender differences in both the prevalence and the clinical manifestations of osteoarthritis (OA) (1). OA appears to be more prevalent in men than women before the age of 50. With the onset of menopause in women, both the prevalence and severity of OA in women increases (1). Small animal models of OA have shown that female mice develop less OA than males, and that ovariectomized (OVX) female mice develop worse OA than female mice with intact ovaries (2). One hypothesis is that estrogen may be a chondro-protective molecule. There has been increasing evidence in recent years that suggest sex hormones and estrogen in particular may be important in maintaining homeostasis of cartilage as well as other articular tissues (3). Notably, the alphaand betareceptors for 17-β estradiol (E2) are both expressed in joint chondrocytes of both male and females, which suggest direct effects on chondrocytes (4). However, the exact cellular and molecular mechanism(s) of E2 in OA chondroprotection are unknown. It is our hypothesis that estrogen acts to inhibit the early chondrocyte apoptosis event which occurs shortly after OA-inducing soft tissue injury.