title: Relaxin and beta-estradiol modulate targeted matrix degradation in specific synovial joint fibrocartilages: progesterone prevents matrix loss.
abstract: Relaxin, a 6-kDa polypeptide hormone, is a potent mediator of matrix turnover and contributes to the loss of collagen and glycosaminoglycans (GAGs) from reproductive tissues, including the fibrocartilaginous pubic symphysis of several species. This effect is often potentiated by beta-estradiol. We postulated that relaxin and beta-estradiol might similarly contribute to the enhanced degradation of matrices in fibrocartilaginous tissues from synovial joints, which may help explain the preponderance of diseases of specific fibrocartilaginous joints in women of reproductive age. The objective of this study was to compare the in vivo effects of relaxin, beta-estradiol, and progesterone alone or in various combinations on GAG and collagen content of the rabbit temporomandibular joint (TMJ) disc fibrocartilage, knee meniscus fibrocartilage, knee articular cartilage, and the pubic symphysis. Sham-operated or ovariectomized female rabbits were administered beta-estradiol (20 ng/kg body weight), progesterone (5 mg/kg), or saline intramuscularly. This was repeated 2 days later and followed by subcutaneous implantation of osmotic pumps containing relaxin (23.3 microg/kg) or saline. Tissues were retrieved 4 days later and analyzed for GAG and collagen. Serum relaxin levels were assayed using enzyme-linked immunosorbent assay. Relaxin administration resulted in a 30-fold significant (p < 0.0001) increase in median levels (range, approximately 38 to 58 pg/ml) of systemic relaxin. Beta-estradiol, relaxin, or beta-estradiol + relaxin caused a significant loss of GAGs and collagen from the pubic symphysis and TMJ disc and of collagen from articular cartilage but not from the knee meniscus. Progesterone prevented relaxin- or beta-estradiol-mediated loss of these molecules. The loss of GAGs and collagen caused by beta-estradiol, relaxin, or beta-estradiol + relaxin varied between tissues and was most prominent in pubic symphysis and TMJ disc fibrocartilages. The findings suggest that this targeted modulation of matrix loss by hormones may contribute selectively to degeneration of specific synovial joints.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, University of Michigan, 1011 North University Avenue, Ann Arbor, MI 48109-1078, USA.
authors.forename: Gihan
authors.initials: G
authors.lastname: Hashem
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hayami
authors.forename: Jean
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Sunil
authors.initials: S
authors.lastname: Kapila
mesh_terms: D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D051445:Fibrocartilage / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism; D007596:Joints / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism; D009994:Osmolar Concentration; D011374:Progesterone / Q000494:pharmacology*; D011631:Pubic Symphysis / Q000378:metabolism; D011817:Rabbits; D012065:Relaxin / Q000097:blood / Q000494:pharmacology*; D013583:Synovial Membrane / Q000378:metabolism*; D019224:Temporomandibular Joint Disc / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D006025:Glycosaminoglycans; D011374:Progesterone; D004958:Estradiol; D012065:Relaxin; D003094:Collagen