Resveratrol Reduces <scp>COMPopathy</scp> in Mice Through Activation of Autophagy

Hecht, Jacqueline; Coustry, Françoise; Veerisetty, Alka C.; Hossain, Mohammad; Posey, Karen L.

doi:10.1002/jbm4.10456

Cited by 16 publications

(39 citation statements)

References 68 publications

(189 reference statements)

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“…Protecting chondrocytes from stress is a central mission in the PSACH treatments. Administration of resveratrol in PSACH patients at an early age (approximately 2 years after birth) may be a promising treatment that activates autophagy and clears mutant-COMP retention [ 138 ]. Anti-inflammation and anti-MMPs reagents may also be important options to reduce the catabolism effects in the PSACH cartilage.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

Cui

Zhang

2022

IJMS

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Cartilage oligomeric matrix protein (COMP) is an extracellular matrix (ECM) glycoprotein that is critical for collagen assembly and ECM stability. Mutations of COMP cause endoplasmic reticulum stress and chondrocyte apoptosis, resulting in rare skeleton diseases. The bouquet-like structure of COMP allows it to act as a bridging molecule that regulates cellular phenotype and function. COMP is able to interact with many other ECM components and binds directly to a variety of cellular receptors and growth factors. The roles of COMP in other skeleton diseases, such as osteoarthritis, have been implied. As a well-established biochemical marker, COMP indicates cartilage turnover associated with destruction. Recent exciting achievements indicate its involvement in other diseases, such as malignancy, cardiovascular diseases, and tissue fibrosis. Here, we review the basic concepts of COMP and summarize its novel functions in the regulation of signaling events. These findings renew our understanding that COMP has a notable function in cell behavior and disease progression as a signaling regulator. Interestingly, COMP shows distinct functions in different diseases. Targeting COMP in malignancy may withdraw its beneficial effects on the vascular system and induce or aggravate cardiovascular diseases. COMP supplementation is a promising treatment for OA and aortic aneurysms while it may induce tissue fibrosis or cancer metastasis.

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Section: Conclusion and Perspectivementioning

confidence: 99%

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

Cui

Zhang

2022

IJMS

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“…For example, resveratrol has neuroprotective properties against various neurological disorders [ 63 ] through the activation of the AMPK autophagy signaling pathway [ 64 ]. Resveratrol could reduce mTORC1 signaling for the activation of autophagy [ 65 ]. In addition, resveratrol can induce autophagy in embryonic stem cells by activating the AMPK pathway and the concomitant suppression of the mTORC1 signaling cascade [ 66 ].…”

Section: Beneficial Components From Natural Products For the Treatmen...mentioning

confidence: 99%

Potential Diets to Improve Mitochondrial Activity in Amyotrophic Lateral Sclerosis

et al. 2022

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Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, the pathogenesis of which is based on alternations in the mitochondria of motor neurons, causing their progressive death. A growing body of evidence shows that more efficient mitophagy could prevent and/or treat this disorder by suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. Mitophagy has been considered one of the main mechanisms responsible for mitochondrial quality control. Since ALS is characterized by enormous oxidative stress, several edible phytochemicals that can activate mitophagy to remove damaged mitochondria could be considered a promising option to treat ALS by providing neuroprotection. Therefore, it is of great significance to explore the mechanisms of mitophagy in ALS and to understand the effects and/or molecular mechanisms of phytochemical action, which could translate into a treatment for neurodegenerative diseases, including ALS.

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“…Previously, we have shown that resveratrol treatment reduces ER stress by promoting autophagy that clears accumulated mutant-COMP from the ER in growth plate chondrocytes of MT-COMP mice [75]. Resveratrol relieved the ER protein accumulation and reduced chondrocyte death, restoring proliferation and supporting limb growth in juvenile MT-COMP mice [75]. Based on these results, resveratrol was administered to determine whether it could prevent and/or reduce joint degeneration in MT-COMP mice.…”

Section: Prevention Of Joint Degeneration In Mt-comp Mice With Resveratrol Treatment or Ablation Of Chopmentioning

confidence: 99%

Joint degeneration in a mouse model of pseudoachondroplasia: ER stress, inflammation and autophagy blockage

et al. 2021

Preprint

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Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia, associated with premature joint degeneration is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur in articular chondrocytes of MT-COMP mice, a murine model of PSACH. The accumulation of mutant-COMP in the ER occurred early in MT-COMP articular chondrocytes and stimulated inflammation (TNFα) at 4 wks. Articular chondrocyte death increased at 8 wks and ER stress through CHOP was elevated by 12 wks. Importantly, blockage of autophagy (pS6), the major mechanism which clears the ER, sustained cellular stress in MT-COMP articular chondrocytes. Degeneration of MT-COMP articular cartilage was similar to that observed in PSACH and was associated with increased MMPs, degradative enzymes. Moreover, chronic cellular stresses stimulated senescence. Senescence-associated secretory phenotype (SASP) may play a role in generating and propagating a pro-degradative environment in the MT-COMP murine joint. The loss of CHOP or resveratrol treatment from birth preserved joint health in MT-COMP mice. Taken together, these results indicate that ER stress/CHOP signaling and autophagy blockage are central to mutant-COMP joint degeneration and MT-COMP mice joint health can be preserved by decreasing articular chondrocyte stress. Future joint sparing therapeutics for PSACH may include resveratrol.

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Resveratrol Reduces COMPopathy in Mice Through Activation of Autophagy

Cited by 16 publications

References 68 publications

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

Potential Diets to Improve Mitochondrial Activity in Amyotrophic Lateral Sclerosis

Joint degeneration in a mouse model of pseudoachondroplasia: ER stress, inflammation and autophagy blockage

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