Diferenciação condrogênica de células-tronco mesenquimais extraídas da medula óssea de ratas hipotireoideas tratadas com Kisspeptina (KP-10)

Abstract

Thyroid hormones play a crucial role in regulating endochondral bone development and growth, including chondrogenesis. Dysfunctions in these hormones can lead to abnormalities in endochondral bone formation and growth, as in the case of hypothyroidism. In this sense, finding a drug to act directly on the cartilage, in order to restore or improve the joint microenvironment, is essential. Kisspeptin is a neuropeptide known for its role in the reproductive system, but recent studies have shown that it can act on cartilage cells from receptors expressed on chondrocytes, promoting improvements in cartilaginous changes resulting from hypothyroidism and osteoarthritis. This study aimed to evaluate the chondrogenic differentiation of MSCs extracted from the bone marrow of hypothyroid rats treated with kisspeptin (Kp-10). oung female rats were divided into 3 experimental groups: control, hypothyroid, and hypothyroid treated with Kp-10. After 3 months, the rats were euthanized to extract the MSCs from the bone marrow. In vitro, chondrogenic differentiation was induced to analyze cell viability through the MTT test, alkaline phosphatase activity, collagen synthesis, cellularity/field, PAS+ matrix and gene expression of chondrogenic markers such as sox-9, collagen type II, collagen X and aggrecan by real-time RT-PCR. Animals in the hypothyroid group showed impaired chondrogenic differentiation of MSCs, evidenced by reduced MTT, increased alkaline phosphatase, decreased collagen synthesis, cellularity, PAS+ matrix and expression of sox-9, collagen II, X and aggrecan. The hypothyroid group treated with Kp-10 revealed innovative discoveries of the action of this neuropeptide on the chondrogenic differentiation of MSCs. A positive impact was observed on both the proliferation and differentiation of chondrocytes. This was evidenced by the increased reduction of MTT in formozan crystals, increased cellularity, PAS+ matrix, in addition to increased expression of sox-9, collagen II and aggrecan. These findings indicate that the neuropeptide Kp-10 may be a promising therapeutic option for the treatment of cartilaginous changes resulting from thyroid dysfunction.