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 β-estradiol. We postulated that relaxin and β-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, β-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 β-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 μg/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. β-estradiol, relaxin, or β-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 β-estradiol-mediated loss of these molecules. The loss of GAGs and collagen caused by β-estradiol, relaxin, or β-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.
Highlights
The development and maintenance of cartilage entails active secretion of macromolecular glycosaminoglycans (GAGs) and collagens by chondrocytes, resulting in an organized extracellular matrix (ECM), which confers specific mechanical and physiologic properties to cartilage [1]
Relaxin administration resulted in a 30-fold significant (p < 0.0001) increase in median levels of systemic relaxin. β-estradiol, relaxin, or β-estradiol + relaxin caused a significant loss of GAGs and collagen from the pubic symphysis and temporomandibular joint (TMJ) disc and of collagen from articular cartilage but not from the knee meniscus
There was a 30-fold increase in median levels of systemic relaxin in all four groups receiving relaxin, which is significantly higher than the changes in sham-operated and ovariectomized normal controls, and in rabbits receiving either β-estradiol or progesterone alone
Summary
The development and maintenance of cartilage entails active secretion of macromolecular glycosaminoglycans (GAGs) and collagens by chondrocytes, resulting in an organized extracellular matrix (ECM), which confers specific mechanical and physiologic properties to cartilage [1]. Chondrocytes play a critical role in the normal remodeling of cartilaginous tissues by expressing tissue-degrading proteinases, primarily those belonging to the matrix metalloproteinase (MMP) family of enzymes [2]. This normal tissue turnover is regulated by many local and systemic agents, including peptide and steroid hormones, and entails the maintenance of a finely tuned balance between matrix synthesis and degradation.
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