Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/β-Catenin Pathway

Zhao, Rongsheng; Zhou, Yalan; Li, Jinqiao; Lin, Junjie; Cui, Wei; Peng, Yan; Bu, Wenqian

doi:10.3389/fphys.2021.639066

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Previous studies have shown that the mRNA and protein levels of ALP in the tibiae and femur of the OVX model were reduced [28,29], which was consistent with our findings. Interestingly, most studies have measured ALP activity in serum and they revealed that ALP activity in serum was increased in OVX model [30][31][32][33][34][35].…”

Section: Discussionsupporting

confidence: 93%

Loss of N-acetylglucosaminyl transferase V is involved in the impaired osteogenic differentiation of bone marrow mesenchymal stem cells

Liu

et al. 2023

Exp. Anim.

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The imbalance of bone resorption and bone formation causes osteoporosis (OP), a common skeletal disorder. Decreased osteogenic activity was found in the bone marrow cultures from MGAT5-deficient mice. We hypothesized that MGAT5 was associated with osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and involved in the pathological mechanisms of osteoporosis. To test this hypothesis, the mRNA and protein expression levels of MGAT5 were determined in bone tissues of ovariectomized (OVX) mice, a well-established OP model, and the role of MGAT5 in osteogenic activity was investigated in murine BMSCs. As expected, being accompanied by the loss of bone mass density and osteogenic markers (runt-related transcription factor 2, osteocalcin and osterix), a reduced expression of MGAT5 in vertebrae and femur tissues were found in OP mice. In vitro, knockdown of MGAT5 inhibited the osteogenic differentiation potential of BMSCs, as evidenced by the decreased expressions of osteogenic markers and less alkaline phosphatase and alizarin red S staining. Mechanically, knockdown of MGAT5 suppressed the nuclear translocation of β-catenin, thereby downregulating the expressions of downstream genes c-myc and axis inhibition protein 2, which were also associated with osteogenic differentiation. In addition, MGAT5 knockdown inhibited bone morphogenetic protein/transforming growth factor (TGF)-β signaling pathway. In conclusion, MGAT5 may modulate the osteogenic differentiation of BMSCs via the β-catenin, BMP2 and TGF-β signals and involved in the process of OP.

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Section: Discussionsupporting

confidence: 93%

Loss of N-acetylglucosaminyl transferase V is involved in the impaired osteogenic differentiation of bone marrow mesenchymal stem cells

Liu

et al. 2023

Exp. Anim.

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“…Furthermore, a sustained increase in the Bcl-2/Bax ratio in the cortical bone of osteoporotic r-irisin-treated mice was found, confirming the extraordinary anti-apoptotic power of this myokine ( Storlino et al, 2020 ). In agreement, Zhao and others reported that irisin can influence osteoblastic cell proliferation through the regulation of the Akt/β-catenin signalling pathway, which is known to be a crucial modulator of the effects of mechanical deformation ( Zhao et al, 2021 ).…”

Section: Discussionsupporting

confidence: 65%

Recombinant irisin prevents cell death and mineralization defects induced by random positioning machine exposure in primary cultures of human osteoblasts: A promising strategy for the osteoporosis treatment

et al. 2023

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Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.

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“…Upon downhill running exercise for 8 weeks, ovariectomized mice have more trabecular bone mineral density and osteoblast number together with increased serum irisin levels and FNDC5 expression in bone tissue as compared to control ovariectomized animals. Administration with irisin receptor agonist cyclo RGDyk protein strengthens the protective effects of exercise on bone tissue integrity in ovariectomized mice [ 107 ].…”

Section: Treatment Options For Osteoporosis Via Mitochondrial Energetics and Rosmentioning

confidence: 99%

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Wang

Chen

et al. 2021

Antioxidants

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Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

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Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/β-Catenin Pathway

Cited by 11 publications

References 38 publications

Loss of N-acetylglucosaminyl transferase V is involved in the impaired osteogenic differentiation of bone marrow mesenchymal stem cells

Loss of N-acetylglucosaminyl transferase V is involved in the impaired osteogenic differentiation of bone marrow mesenchymal stem cells

Recombinant irisin prevents cell death and mineralization defects induced by random positioning machine exposure in primary cultures of human osteoblasts: A promising strategy for the osteoporosis treatment

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

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