Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation

Zhang, Mian; Zhang, Jing; Lü, Lei; Qiu, Zhongying; Zhang, Xu; Yu, Shuxun; Wu, Yaoping; Wang, Meiqing

doi:10.1007/s10495-013-0811-0

Cited by 45 publications

(50 citation statements)

References 46 publications

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“…Recent studies have demonstrated that autophagy is involved in certain bone and cartilage diseases, such as cervical disc degeneration (42), cartilage degeneration of the temporomandibular joint (23), degradation of Meckel's cartilage (43) and OA (44). However, the results regarding changes in autophagy and the specific role of autophagy in the progression of OA are sometimes contradictory (25,26).…”

Section: Discussionmentioning

confidence: 99%

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis

Cheng

Meng

et al. 2017

International Journal of Molecular Medicine

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Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.

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Section: Discussionmentioning

confidence: 99%

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis

Cheng

Meng

et al. 2017

International Journal of Molecular Medicine

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“…Aging is an important risk factor for the development of OA and is associated with the progressive accumulation of damaged macromolecules and organelles in somatic cells [27], potentially mediated by downregulation of the autophagic disposal of such damaged cellular components [28]. Autophagy-related proteins unc-51-like autophagy activating kinase 1 (ULK1), Beclin1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) are reported to be expressed at high levels in healthy human cartilage [25,29,30], however, their expression decreases during OA [25,26]. Mechanistic target of rapamycin complex 1 (mTORC1) intracellular signalling pathway is an autophagic regulator that when inhibited activates the process of autophagy [31].…”

Section: Discussionmentioning

confidence: 99%

AntimiR-30b Inhibits TNF-α Mediated Apoptosis and Attenuated Cartilage Degradation through Enhancing Autophagy

Chen

Jin

2016

Cell Physiol Biochem

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Objective: Cell death plays an important role in the pathology associated with inflammatory diseases such as osteoarthritis. It has been reported that autophagy can protect cells against tumour necrosis factor-α (TNF-α)-induced apoptosis. This study aimed to determine the potential role of microRNA-30b (miR-30b) in TNF-α-induced apoptosis, autophagy and differentiation in the chondrogenic ADTC5 cell line. Methods: To analyse the effect of TNF-α on the viability of ADTC5 cells, cell counting kit-8 and Hoechst 33342 staining were employed and the expression levels of caspase-3 and -9 were assessed. Autophagy was examined by analysing the levels of LC3B-II and p62 and quantitating GFP-LC3B by fluorescence microscopy. A luciferase reporter assay investigated the putative binding sites of miR-30b. The effects of miR-30b and antimiR-30b on autophagy, apoptosis and osteogenic differentiation of TNF-α-treated cells were determined by autophagosome, apoptosis and alkaline phosphatase assays, respectively. Results: TNF-α exposure decreased cell viability, increased apoptosis and positively regulated autophagy in ADTC5 cells. A direct interaction was detected between miR-30b and the mRNA 3ʹ-UTRs of autophagy genes BECN1 and ATG5. Overexpression of miR-30b downregulated autophagy genes and upregulated pro-apoptotic gene expression in TNF-α-treated cells, while treatment with antimiR-30b had the inverse effect. Overexpression of miR-30b also downregulated ECM degradation and anti-miR-30b reverse TNF-α-induced ECM degradation. Conclusions: Anti-miR-30b enhanced autophagy and attenuated cartilage degradation and played a protective role in TNF-α-induced apoptosis of ATDC5 cells. Anti-miR-30b may therefore elevate cellular survival during inflammation and has therapeutic potential for inflammatory diseases such as osteoarthritis.

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“…Indeed, in a rat model of biomechanically-induced degenerative cartilage of the temporomandibular joint (TMJ), some have proposed that autophagy is induced as an early event post injury, as observed by increased autophagosome detection by TEM, increased levels of beclin1 and LC3, as well as decreased mTOR and MAP4K3 activities [245]. In contrast, in bovine and human cartilage explants subjected to mechanical impact, autophagy was inhibited, and rapamycin treatment of mechanically-injured explants induced the expression of autophagy regulators and prevented cell death and glycosaminoglycans (GAG) release [246].…”

Section: Cell Death Regulators In Chondrocytesmentioning

confidence: 99%

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Charlier

Relić

Deroyer

et al. 2016

IJMS

266

220

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Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1β (IL-1β), Tumor Necrosis factor-α (TNF-α), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1α/HIF-2α imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression.

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Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation

Cited by 45 publications

References 46 publications

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis

AntimiR-30b Inhibits TNF-α Mediated Apoptosis and Attenuated Cartilage Degradation through Enhancing Autophagy

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

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