title: In vivo effects of ovarian steroid hormones on the expressions of estrogen receptors and the composition of extracellular matrix in the anterior cruciate ligament in rats.
abstract: 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.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Toru
authors.initials: T
authors.lastname: Morihara
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kajikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Oshima
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006614:Hindlimb; D007150:Immunohistochemistry; D064235:Matrilin Proteins; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013264:Stifle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D011374:Progesterone; D004958:Estradiol; D003094:Collagen