Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles

Liu, Y.-D.; Yang, Hong; Liao, Lin; Jiao, Kai; Zhang, H.-Y.; Lü, Lei; Zhang, M.; Zhang, J.; He, Jianjun; Wu, Yaoping; Chen, Di; Wang, M.-Q.

doi:10.1016/j.joca.2015.07.022

Cited by 21 publications

(19 citation statements)

References 41 publications

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“…The cellular zonal boundary of mouse TMJ cartilage is not as morphologically typical as that in rats. However, our previous study revealed that the TMJs of rats and mice respond to UAC stimulation in a very similar manner considering the cartilage and subchondral bone phenotypes and chondrocyte terminal differentiation [23,24,25,26,27,28,29,30,31,32]. Briefly, the UAC-induced TMJ OA-like changes predominantly affected the deep zone cartilage.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have indicated that TMJ OA induced by interrupted dental occlusion undergoes different pathological processes as compared to knee OA [22]. Recently, we created a rodent model by exposing the animals to an aberrant biomechanical dental occlusion, termed unilateral anterior crossbite (UAC), which simulated clinical abnormal dental occlusion and caused a series of TMJ OA-like changes without surgical damage [23,24,25,26,27,28,29,30]. Our latest research suggested that one of the typical changes in chondrocytes in UAC rat TMJ OA cartilage was abnormal differentiation, starting from the injured deep zone and then expanding to the superficial zone [26].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism

Yang

Zhang

Qian

et al. 2019

IJMS

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The temporomandibular joint (TMJ), which is biomechanically related to dental occlusion, is often insulted by osteoarthritis (OA). This study was conducted to clarify the relationship between Indian hedgehog (Ihh) and parathyroid hormone receptor 1 (PTH1R) signaling in modulating the enhanced chondrocyte terminal differentiation in dental stimulated TMJ osteoarthritic cartilage. A gain- and loss-of-function strategy was used in an in vitro model in which fluid flow shear stress (FFSS) was applied, and in an in vivo model in which the unilateral anterior cross-bite (UAC) stimulation was adopted. Ihh and PTH1R signaling was modulated through treating the isolated chondrocytes with inhibitor/activator and via deleting Smoothened (Smo) and/or Pth1r genes in mice with the promoter gene of type 2 collagen (Col2-CreER) in the tamoxifen-inducible pattern. We found that both FFSS and UAC stimulation promoted the deep zone chondrocytes to undergo terminal differentiation, while cells in the superficial zone were robust. We demonstrated that the terminal differentiation process in deep zone chondrocytes promoted by FFSS and UAC was mediated by the enhanced Ihh signaling and declined PTH1R expression. The FFSS-promoted terminal differentiation was suppressed by administration of the Ihh inhibitor or PTH1R activator. The UAC-promoted chondrocytes terminal differentiation and OA-like lesions were rescued in Smo knockout, but were enhanced in Pth1r knockout mice. Importantly, the relieving effect of Smo knockout mice was attenuated when Pth1r knockout was also applied. Our data suggest a chondrocyte protective effect of suppressing Ihh signaling in TMJ OA cartilage which is dependent on PTH1R signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism

Yang

Zhang

Qian

et al. 2019

IJMS

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“…P65 is a critical active subunit in NF-jB signalling in multiple cell types [36]. Liu found that the percentages of phosphorylated p65 were significantly increased in TMJ-OA mice [37]. Chen showed that p65-specific siRNA could suppress the induction of IL-1b and delay the cartilage degradation in OA model in early-phase [9].…”

Section: Discussionmentioning

confidence: 99%

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL‐1β/NF‐κB pathway

Wang¹,

Huang²,

Zhou³

et al. 2017

J Cellular Molecular Medi

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The osteoarthritis (OA) progression is now considered to be related to inflammation. Anemonin (ANE) is a small natural molecule extracted from various kinds of Chinese traditional herbs and has been shown to inhibiting inflammation response. In this study, we examined whether ANE could attenuate the progression of OA via suppression of IL‐1β/NF‐κB pathway activation. Destabilization of the medial meniscus (DMM) was performed in 10‐week‐old male C57BL/6J mice. ANE was then intra‐articularly injected into joint capsule for 8 and 12 weeks. Human articular chondrocytes and cartilage explants challenged with interleukin‐1β (IL‐1β) were treated with ANE. We found that ANE delayed articular cartilage degeneration in vitro and in vivo. In particular, proteoglycan loss and chondrocyte hypertrophy were significantly decreased in ANE ‐treated mice compared with vehicle‐treated mice. ANE decreased the expressions of matrix metalloproteinase‐13 (MMP13), A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), collagen X (Col X) while increasing Aggrecan level in murine with DMM surgery. ANE treatment also attenuated proteoglycan loss in human cartilage explants treated with IL‐1β ex vivo. ANE is a potent protective molecule for OA; it delays OA progression by suppressing ECM loss and chondrocyte hypertrophy partially by suppressing IL‐1β/NF‐κB pathway activation.

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“…We recently reported that fluid flow shear stress (FFSS) induced TMJ chondrocyte death in vitro [5][6][7]. We also developed an in vivo abnormal dental occlusion termed unilateral anterior cross (UAC) model and demonstrated that it induced chondrocyte death and OA-like lesions in TMJ cartilage in rats and mice [7][8][9][10][11]. These in vitro and in vivo models are useful tools to facilitate the investigation of molecular mechanisms through which abnormal biomechanical forces induce chondrocyte death and the onset of TMJ OA.…”

Section: Introductionmentioning

confidence: 99%

MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint

et al. 2019

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A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA.

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Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles

Cited by 21 publications

References 41 publications

Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism

Inhibition of Ihh Reverses Temporomandibular Joint Osteoarthritis via a PTH1R Signaling Dependent Mechanism

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL‐1β/NF‐κB pathway

MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint

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