FSTL1 Can Be a Promising Target in TMJ Osteoarthritis via Regulating Chondrocyte Mitophagy and Apoptosis.

Abstract

Background: Previous studies have shown that follistatin-like protein 1 (FSTL1) is elevated in the synovial fluid of osteoarthritis and whether it is associated with disease development progress in cartilage degeneration is still unclear. The experiment was performed to explore the effect and mechanism of FSTL1 on chondrocyte degeneration and its further impaction in osteoarthritis as well as its treatment method.

Methods: The patients who were diagnosed with temporomandibular joint (TMJ) disc displacement and osteoarthritis (OA) group was divided into 2 groups, anterior disc displacement (ADD) without bone resorption and ADD with bone resorption group according to the radiologic examination. The ELISA kit was used to determine the expression level of FSTL1 in patients TMJ environment. The function of FSTL1 in promoting chondrocyte degeneration was tested by quantitative reverse transcription polymerase chain reaction (Rt-qPCR) and western blot. The chondrocyte apoptosis and mitophagy were further test by flow cytometry and mitosox staining by upregulating and downregulating of FSTL1. In the end, the effectiveness of regulating FSTL1 in OA procedure was further validated by hematoxylin-eosin (HE), safranin O, and immunohistochemical (IHC) staining in vivo.

Results: There were 56 samples collected from the patients were included into this study. According to the ELISA results, FSTL1 expression levels of ADD without bone resorption groups were significantly lower than that in ADD with bone resorption group. Furthermore, the rate of cell apoptosis cells and the mitophagy procedure were highly activated when FSTL1 was upregulated. The morphology analysis of mitochondria showed significant changes when FSTL1 was highly upregulated in vitro. The in vivo and in vitro experiments showed that suppressing FSTL1 could alleviate the cartilage degeneration in TMJ OA progression.

Conclusions: To sum up, upregulated expression level of FSTL1 in synovial fluid promoted the progression of TMJ OA by upregulating accelerating the chondrocyte apoptosis and mitophagy, and suppressing the FSTL1 in TMJ can rescue the OA progression. Therefore, it may be a promising result to consider the FSTL1 as a therapeutic target in the future.