Immunohistochemical analysis of the effects of estrogen on intraarticular neurogenic inflammation in a rat anterior cruciate ligament transection model of osteoarthritis

Synovitis is considered as one of the factors associated with the pathogenesis of osteoarthritis (OA). There is currently a significant amount of research linking estrogen deficiencies with the development of OA in estrogen-deficient women, including postmenopausal women; however, the exact etiology remains unclear. Various neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been shown to contribute to synovitis in OA joints, and the influence of estrogen on the expressions of SP and CGRP in the synovium of OA joints has been noted. After ovariectomy (OVX) followed by estradiol (E2) replacement, 24 female rats were divided into three groups: OVX group, OVX + E2 replacement group (E2 group), and a sham group. All rats underwent transection of the anterior cruciate ligament at the same time. After 30 days, the histological findings of knee joints by hematoxylin-eosin staining and immunofluorescence staining of protein gene product 9.5 (pan-neuronal marker), SP, and CGRP were compared among experimental groups. The degree of synovitis in the OVX group was higher than in the E2 and sham groups. No significant differences in the density of protein gene product 9.5-immunoreactive nerve fibers were observed among the three experimental groups, but the density of SP- or CGRP-immunoreactive nerve fibers in the OVX group was significantly higher than in the E2 and sham groups. These findings suggest that estrogen partly regulates intraarticular neurogenic inflammation in OA joints by modulating the expressions of neuropeptides in the synovium.