Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice

Abstract

Recent emerging data indicate that the increase in the expression and activity of the transforming growth factor beta 1 (Tgf-β1) signaling may have detrimental effect to mature articular cartilage of knee joints. However, there is no information about whether or not this is the case in condylar cartilages. The objective of this study is to investigate the protein expression and activity of Tgf-β1 signaling in degenerative condylar cartilages. We also investigate biological effects of the conditional deletion of transforming growth factor receptor type II (Tgfbr2) in condylar cartilage of adult mice after a partial discectomy. Two mouse models of osteoarthritis (OA) were used to examine protein expressions of Tgf-β1 and p-Smad2/3 in condylar cartilages at early degenerative stages. In addition, cartilage specific Tgfbr2-deficient adult mice were subjected to a partial discectomy. The morphological condition of condylar cartilages was evaluated in mice at 4 and 12 weeks after the surgery. We found that protein levels of Tgf-β1 and p-Smad2/3 were increased in the degenerative condylar cartilage of the mouse models. The conditional removal of Tgfbr2 in mature condylar cartilage significantly delayed the progressive progression of the cartilage degeneration induced by a partial discectomy. We conclude that the increase in the expression and activity of Tgf-β1 signaling may have detrimental effect to mature condylar cartilages. Therefore, inhibition of Tgf-β1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

“…The expression and activity of TGF-β1 signalling significantly increase in the cartilage at the early degenerative stage of OA. 30 This observation indicates that abnormal activation of TGF-β1 signalling induces cartilage degeneration in TMJ-OA.…”

“… 29 Therefore, the interruption of TGF-β1 signalling in articular cartilage leads to articular and condylar cartilage degeneration. 30 Furthermore, a high concentration of TGF-β1 in subchondral bone was found in an anterior cruciate ligament transection (ACLT) OA mouse model. 31 The overexpression TGF-β1 signalling in subchondral bone leads to abnormal remodelling and is harmful to cartilage integrity.…”

Two-photon fluorescence and second harmonic generation characterization of extracellular matrix remodeling in post-injury murine temporomandibular joint osteoarthritis

“…TGF-β1 stimulates a fibrotic phenotype in chondrocytes, and TGF-β1 knockout mice have attenuated OA progression [ 43 , 44 ]. TGF-β1 is elevated in TMJ-OA condyles and believed to play an important role in the progression of TMJ-OA [ 45 ]. Taken together, there is strong support for early stage TMJ-OA being associated with a fibrotic superficial layer matrix rich in type I and III collagen.…”

TGF‐β/SMAD signaling inhibits intermittent cyclic mechanical tension‐induced degeneration of endplate chondrocytes by regulating the miR‐455‐5p/RUNX2 axis

“…TGF‐β is considered one of the most important growth factors regulating the homeostasis of chondrocytes. It has complex and diverse biological effects that are opposing in regulation of the proliferation of chondrocytes, it can either inhibit or enhance their proliferation . Different concentrations of TGF‐β also have opposite effects on proliferation.…”