Efeitos da kisspeptina (kp10) sobre as alterações cartilagíneas causadas pelo hipotireoidismo em ratas adultas

Abstract

Thyroid hormones T3 (3,5,3'-triiodo-l-thyronine) and T4 (3,5,3',5'-tetraiodo-l-thyroxine) are essential during the development and growth of cartilaginous tissue. The T3 hormone is required for epiphyseal plate differentiation and maintenance of articular cartilage to occur. In hypothyroidism, the reduction of T3 and T4 results in cartilage abnormalities with manifestations at all ages. As thyroid function is related to the control of gonadotropins and prolactin (PRL), it is likely that these changes may result from the hyperprolactinemia observed in hypothyroidism. Hyperprolactinemia negatively modulates the secretion of kisspeptin (Kp10), a neuropeptide produced in the hypothalamus, which is involved in the release of gonadotropin-regulating hormone (GnRH) that acts on several neuroendocrine regulatory systems. This study aimed to evaluate the effects of treatment with Kp10 on cartilaginous changes caused by hypothyroidism in adult female rats, as well as the presence of the kisspeptin receptor (GPR54) in the chondrocytes that make up the articular cartilage and the epiphyseal plate. of rats. The results demonstrate the marking of GPR54 receptors in the chondrocytes of both the articular cartilage and the epiphyseal plate, and the most intense marking was observed in the middle and proliferative layers, respectively. The animals with hypothyroidism showed a reduction in the thickness of the articular cartilage and the epiphyseal plate, leading to a disorganization of the chondrocytes. Meanwhile, the hypothyroid animals treated with Kp10, showed an increase in the thickness of the joint cartilage and the epiphyseal plate, in addition to a reorganization of the chondrocytes similar to the control group. It was also observed that during this reorganization there was an increase in the superficial and deep zone of the articular cartilage, as well as an increase in the hypertrophic zone of the epiphyseal plate. In the histochemical analysis of the cartilaginous matrix using safranin-O staining, a deficiency of glycosaminoglycans was observed in hypothyroid animals and the recovery of these components after treatment with Kp10. Another data that corroborates this information is that in the analysis of aggrecan gene expression by means of RT-PCR, a reduction was observed in the hypothyroid group in relation to the control and an increase in the same after treatment with Kp10. Other important genes for chondrogenesis, such as Sox-9, Runx-2, collagen type II, X and vascular endothelial growth factor (VEGF) were also evaluated. It was observed that the gene expression of sox-9 was higher in the hypothyroid group treated with Kp10 compared to the control and hypothyroid group. In the analysis of runx-2, collagen X and VEGF, there was a lower gene expression in the hypothyroid group compared to the control and an increase of these genes in the hypothyroid group treated with Kp10 compared to the hypothyroid group. Only collagen II showed no significant difference between groups. Thus, the results of this study suggest that Kp10 stimulates the proliferation and differentiation of chondrocytes in the joint cartilage and in the epiphyseal plate of hypothyroid rats, reversing the effects observed by the reduction of thyroid hormones.