Irisin Prevents Disuse-Induced Osteocyte Apoptosis

Storlino, Giuseppina; Colaianni, Graziana; Sanesi, Lorenzo; Lippo, Luciana; Brunetti, Giacomina; Errede, Mariella; Colucci, Silvia; Passeri, Giovanni; Grano, Maria

doi:10.1002/jbmr.3944

Cited by 91 publications

(85 citation statements)

References 33 publications

(84 reference statements)

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“…Increase Cx43 expression; promote gap junction elongate; maintain the survival of osteocytes 59 Irisin Prevent apoptosis of osteocytes through excise 57,58,91…”

Section: Fgf7mentioning

confidence: 99%

“…In addition, it was reported that integrins, tethering osteocytes to the canalicular wall, function as a mediator in the interaction of osteocytic processes with extracellular matrix in vivo. Hence, it has been assumed that PFF in osteocytic LCN could give rise to tension on the integrins, which in turn stimulate integrin signaling to prevent osteocyte apoptosis 55,57 . Also, it was found that the level of irisin, a peptide cleaved from Fndc5, is increased in the circulation during and following exercise in mice and humans, and its receptor, an integrin alphaV/beta 5 (αV/β5), is characterized in osteocytes 58 .…”

Section: Unloading Nutrition Deprivation and Hypoxiamentioning

confidence: 99%

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Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Wang

2020

Cell Death Dis

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Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.

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“…Increase Cx43 expression; promote gap junction elongate; maintain the survival of osteocytes 59 Irisin Prevent apoptosis of osteocytes through excise 57,58,91…”

Section: Fgf7mentioning

confidence: 99%

Section: Unloading Nutrition Deprivation and Hypoxiamentioning

confidence: 99%

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Wang

2020

Cell Death Dis

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“…Irisin increases the myoblast differentiation of myogenic progenitor cells and promotes the regeneration capacity of notexin-injured skeletal muscle [20]. FNDC5 knockout compromises estrogen deficiency-mediated osteocytic osteolysis and trabecular bone loss [21], as well as downregulating unloading-induced osteocyte apoptosis and osteoporosis development [22]. Irisin recombinant protein increases growth and ECM accumulation in human osteoarthritic chondrocytes [23].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Kuo

et al. 2020

Antioxidants

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Compromised autophagy and mitochondrial dysfunction downregulate chondrocytic activity, accelerating the development of osteoarthritis (OA). Irisin, a cleaved form of fibronectin type III domain containing 5 (FNDC5), regulates bone turnover and muscle homeostasis. Little is known about the effect of Irisin on chondrocytes and the development of osteoarthritis. This study revealed that human osteoarthritic articular chondrocytes express decreased level of FNDC5 and autophagosome marker LC3-II but upregulated levels of oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) and apoptosis. Intra-articular administration of Irisin further alleviated symptoms of medial meniscus destabilization, like cartilage erosion and synovitis, while improved the gait profiles of the injured legs. Irisin treatment upregulated autophagy, 8-OHdG and apoptosis in chondrocytes of the injured cartilage. In vitro, Irisin improved IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production by chondrocytes. Irisin also reversed Sirt3 and UCP-1 pathways, thereby improving mitochondrial membrane potential, ATP production, and catalase to attenuated IL-1β-mediated reactive oxygen radical production, mitochondrial fusion, mitophagy, and autophagosome formation. Taken together, FNDC5 loss in chondrocytes is correlated with human knee OA. Irisin repressed inflammation-mediated oxidative stress and extracellular matrix underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. Our analyses shed new light on the chondroprotective actions of this myokine, and highlight the remedial effects of Irisin on OA development.

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“…Significantly, it is reported that irisin inhibited adipogenesis through regulating the Wnt/β-catenin signaling pathway [37]. In addition, Wnt antagonists sclerostin and dickkopf-1 were downregulated in MLO-Y4 cells after treatment with r-irisin [45]. Interestingly, our data demonstrated that r-irisin promoted β-catenin mRNA and protein expression ( Figure 5a).…”

Section: Discussionmentioning

confidence: 52%

“…To investigate the mechanism underlying how r-irisin increased osteoblast differentiation, we analyzed signaling pathways which irisin regulated based on reported studies, and found that irisin could modulate Notch [43], focal adhesion kinase (FAK) -extracellular signal-regulated kinase (Erk) -mitogen-activated protein (MAP) [23,25,44,45], reactive oxygen species (ROS) [46,47], phosphatidylinositol-3-kinase (PI3K) -v-akt murine thymoma viral oncogene homolog 1(AKT) [48], and Wnt/β-catenin [27,37,45] signaling pathways. Significantly, it is reported that irisin inhibited adipogenesis through regulating the Wnt/β-catenin signaling pathway [37].…”

Section: Discussionmentioning

confidence: 99%

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Chen

Zhang

Zhao

et al. 2020

IJMS

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Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.

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Irisin Prevents Disuse-Induced Osteocyte Apoptosis

Cited by 91 publications

References 33 publications

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

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

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

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