As such, OA is a leading cause of disability in North America affecting 1 in 6 adults. For the patient, this manifests as joint pain and stiffness, and reduced mobility and quality of life. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, meniscal damage, synovial inflammation and osteophyte formation at the joint margins. Understanding the molecular mechanisms underlying the development of OA is essential for the development of individualized, sex-specific treatments in this age of personalized medicine. Together these data highlight sexual dimorphism in the EGFR/integrin α1β1 signaling axis and underline the need for further investigation into the role of ERs in this biological paradigm. Finally, we show sexual dimorphism in ROS and 3-nitrotyrosine production, but surprisingly not in pEGFR expression. In addition, we found that itga1 influenced ERα and ERβ expression in femoral cartilage from female mice, and that ERα and ERβ were coexpressed as well as colocalized in chondrocytes. We show that ROS-producing chondrocytes are more abundant in female itga1-null compared to wild-type mice ex vivo however, itga1 had limited influence on the percent of chondrocytes stained positively for 3-nitrotyrosine or pEGFR in situ. We further hypothesized that chondrocyte expression of ERα and ERβ would be greater in females compared to males, with a greater effect seen in itga1-null compared to wild-type mice.įemoral and tibial cartilage of male and female, wild-type and itga1-null mice were processed for ex vivo confocal imaging of ROS, immunohistochemical analysis of 3-nitrotyrosine, or immunofluorescence of pEGFR and ERα and ERβ. We hypothesized that integrin α1β1 would decrease ROS production and pEGFR and 3-nitrotyrosine expression, with this effect being greater in females. Furthermore, chondrocyte expression of estrogen receptor (ER) α and ERβ was measured to investigate the mechanism for sexual dimorphism in the EGFR/integrin α1β1 signaling axis. The aim of this study, therefore, was to measure the impact of itga1 on chondrocyte EGFR activity and downstream reactive oxygen species (ROS) production in male and female mice. ![]() Integrin α1β1 offers this protection by dampening epidermal growth factor receptor (EGFR) signaling, and its effects are more robust in females compared to males. ![]() One potential target is integrin α1β1 that protects against OA when it is upregulated by chondrocytes early in the disease process. ![]() A need remains for the discovery of new molecular targets in cartilage for pharmaceutical intervention of OA. Osteoarthritis (OA) is a debilitating disease involving cartilage degradation.
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