Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy

Wang, Feng‐Sheng; Kuo, Chung-Wen; Ko, Jih‐Yang; Chen, Yu‐Shan; Wang, Shaoyu; Ke, Huei-Jing; Kuo, Pei-Chen; Lee, Chin-Huei; Wu, Jian-Ching; Lu, Wen-Bin; Tai, Ming‐Hong; Jahr, Holger; Lian, Wei

doi:10.3390/antiox9090810

Cited by 97 publications

(86 citation statements)

References 56 publications

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“…When Fndc5 expression was suppressed, on the other hand, the consequential PGC-1α defects lowered the abundance and size of mitochondria [ 87 ]. Irisin was also able to retain mitochondrial biogenesis, dynamics, and autophagic program in chondrocytes to repress inflammation-mediated oxidative stress and extracellular matrix underproduction [ 88 ]. Interestingly, irisin inhibits mitochondrial fission via the JNK-LATS2 pathway in cardiomyocytes [ 89 ] and hepatocytes [ 90 ] when excessive fission occurred during inflammation.…”

Section: Myokines and Mitochondrial Dynamicsmentioning

confidence: 99%

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Pang¹,

Chan²,

Chan³

2021

Antioxidants

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Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.

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Section: Myokines and Mitochondrial Dynamicsmentioning

confidence: 99%

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Pang¹,

Chan²,

Chan³

2021

Antioxidants

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“…Irisin repressed inflammation-mediated oxidative stress and ECM underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. 175 Recently, the small molecule kartogenin regulating the core binding factor subunit (CBF)β-RUNX1 pathway was reported to promote the differentiation of bone marrow (BM)-derived MSCs (BM-MSCs) into chondrocytes in vitro. Kartogenin exhibited chondroprotection when injected i.a.…”

Section: Anabolic Factors: Growth Factors and Hormones Hormone Analomentioning

confidence: 99%

“…Irisin repressed inflammation-mediated oxidative stress and ECM underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. 175 …”

Section: Anabolic Factors: Growth Factors and Hormones Hormone Analomentioning

confidence: 99%

Experimental Therapeutics for the Treatment of Osteoarthritis

Schulze‐Tanzil

2021

JEP

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Osteoarthritis (OA) therapy remains a large challenge since no causative treatment options are so far available. Despite some main pathways contributing to OA are identified its pathogenesis is still rudimentary understood. A plethora of therapeutically promising agents are currently tested in experimental OA research to find an opportunity to reverse OA-associated joint damage and prevent its progression. Hence, this review aims to summarize novelly emerging experimental approaches for OA. Due to the diversity of strategies shown only main aspects could be summarized here including herbal medicines, nanoparticular compounds, growth factors, hormones, antibody-, cell-and extracellular vesicle (EV)-based approaches, optimized tools for joint viscosupplementation, genetic regulators such as si-or miRNAs and promising combinations. An abundant multitude of compounds obtained from plants, environmental, autologous or synthetic sources have been identified with anabolic, anti-inflammatory,-catabolic and anti-apoptotic properties. Some ubiquitous signaling pathways such as wingless and Integration site-1 (Wnt), Sirtuin, Tolllike receptor (TLR), mammalian target of rapamycin (mTOR), Nuclear Factor (NF)-κB and complement are involved in OA and addressed by them. Hyaluronan (HA) provided benefit in OA since many decades, and novel HA formulations have been developed now with higher HA content and long-term stability achieved by cross-linking suitable to be combined with other agents such as components from herbals or chemokines to attract regenerative cells. pH-or inflammation-sensitive nanoparticular compounds could serve as versatile slowrelease systems of active compounds, for example, miRNAs. Some light has been brought into the intimate regulatory network of small RNAs in the pathogenesis of OA which might be a novel avenue for OA therapy in future. Attraction of autologous regenerative cells by chemokines and exosome-based treatment strategies could also innovate OA therapy.

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“…Surgically induced OA models are representative of post-traumatic OA, but most OA cases are not secondary to trauma. Chemical-intervention-induced cartilage degradation triggers an acute episode of chondrocyte death, extracellular matrix (ECM) loss, and joint inflammation, which do not usually occur in primary OA [ 42 , 43 ]. Dunkin–Hartley (DH) guinea pigs develop OA spontaneously in as early as three months of age and are proposed as a practical model for investigating the progression of primary OA [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Intra-Articular Injection of (−)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

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Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy

Cited by 97 publications

References 56 publications

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Experimental Therapeutics for the Treatment of Osteoarthritis

Intra-Articular Injection of (−)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis

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