Yoshida Atsuhiko, Morihara Toru, Kajikawa Yoshiteru, Arai Yuji, Oshima Yasushi, Kubo Toshikazu, Matsuda Ken-ichi, Sakamoto Hirotaka, Kawata Mitsuhiro
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Connect Tissue Res. 2009;50(2):121-31. doi: 10.1080/03008200802531287.
Female athletes have a significantly higher rate of anterior cruciate ligament (ACL) injury than their male counterparts. Sex steroid hormones are considered to have an influence as risk factors for female ACL injuries. We hypothesized that estrogen and progesterone have specific and synergistic influences on the composition of extracellular matrix in ACL. By ovariectomy (OVX) followed by subcutaneous estradiol (E2) and/or progesterone (P4) replacement, 40 female rats were divided into 5 groups: E2, P4, combined E2 and P4 (EP), OVX control, and sham group. After 30 days, using undecalcified sections of knee joints in conjunction with immunofluorescence staining of estrogen receptor alpha and beta (ERalpha and ERbeta), collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP), the immunoreactivities of these proteins in two distinct parts of ACL, proximal and middle portions, were compared semiquantitatively among experimental groups. By E2 replacement, the expressions of ERalpha in ACL fibroblasts were elevated compared to the OVX group. At the proximal portion, the immunoreactivities of type 1 collagen by E2 replacement, type 3 collagen by P4 replacement, and COMP by E2 or P4 replacement were significantly reduced. At the middle portion, the immunoreactivity of type 3 collagen was significantly elevated by E2 replacement. However, no differences were observed between the sham and OVX groups. These findings suggest that ACL is ER-dependent and that ovarian hormones alter ligament tissue composition, especially at the proximal portion. Female hormonal influences are partly involved in the biological properties of ACL.
女性运动员前交叉韧带（ACL）损伤的发生率明显高于男性运动员。性类固醇激素被认为是女性ACL损伤的危险因素。我们假设雌激素和孕激素对ACL细胞外基质的组成具有特定的协同影响。通过卵巢切除术（OVX），然后皮下注射雌二醇（E2）和/或孕激素（P4）进行替代，将40只雌性大鼠分为5组：E2组、P4组、E2和P4联合组（EP组）、OVX对照组和假手术组。30天后，使用膝关节未脱钙切片结合雌激素受体α和β（ERα和ERβ）、1型和3型胶原蛋白以及软骨寡聚基质蛋白（COMP）的免疫荧光染色，在实验组之间对ACL两个不同部位（近端和中部）这些蛋白质的免疫反应性进行半定量比较。通过E2替代，与OVX组相比，ACL成纤维细胞中ERα的表达升高。在近端部分，E2替代导致的1型胶原蛋白免疫反应性、P4替代导致的3型胶原蛋白免疫反应性以及E2或P4替代导致的COMP免疫反应性均显著降低。在中部，E2替代使3型胶原蛋白的免疫反应性显著升高。然而，假手术组和OVX组之间未观察到差异。这些发现表明ACL是雌激素依赖性的，卵巢激素会改变韧带组织组成，尤其是在近端部分。女性激素影响部分参与了ACL的生物学特性。
