Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes

Abstract

Integrin alpha1beta1 protects against OA development when it is upregulated in the early stages of disease development. One possible mechanism through which integrin alpha1beta1 affords this protection is through suppression of growth factor receptor signaling pathways, including EGFR. The interplay of integrin alpha1beta1 and EGFR in post-traumatic OA is sex-dependent, suggesting ERs may also participate. The purpose of this thesis was to evaluate the percent of knee chondrocytes immunostained for pEGFR, 3-nitrotyrosine, ERalpha and ERbeta in itga1-null and wild type mice. We show that integrin alpha1beta1 had limited influence on the percent of chondrocytes stained positively for pEGFR or 3-nitrotyrosine. In contrast, we found that integrin alpha1beta1 did influence ERalpha and beta expression that were co-expressed as well as co-localized in chondrocytes. Understanding the molecular mechanisms underlying the development of OA is essential for the development of effective, individualized, sex-specific treatments in this age of personalized medicine.