Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice

He, Zihao; Li, Hanjun; Han, Xing; Zhou, Feng; Du, Jingke; Yang, Yiqi; Xu, Qi; Zhang, Shuhong; Zhang, Shuangyan; Zhao, Ning; Yan, Mi; Yu, Zhifeng

doi:10.1016/j.bone.2020.115573

Cited by 51 publications

(45 citation statements)

References 53 publications

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“…This was reversed however in the group of ACLT mice that were injected with r-irisin at a daily dose of 100 µg/kg b.w. for 4 weeks (Table 5) [70]. Microtomography suggested that the irisin injections rescued the damaging effects of ACLT in the subchondral and in the tibial trabecular bone as confirmed with bone histomorphometry staining.…”

Section: Role Of Irisin On Bone Homeostasis: In Vivo Evidencementioning

confidence: 69%

“…Exposure of MLO-Y4 osteocyte cells to irisin (100 ng/mL) for 24 h resulted in significantly reduced cyclic stretching-induced apoptosis and increased osteocyte proliferation [70]. Irisin treatment significantly reduced sclerostin mRNA level and increased the ratio of OPG/RANKL, suggesting improved bone remodeling.…”

Section: Osteocytesmentioning

confidence: 93%

“…The subchondral bone area had less ACLT-stimulated TRAP+ stained osteoclasts in the irisin group as compared the vehicle control group (Figure 4). Immunohistochemical staining showed decreased expression of MMP-13 and caspase 3 suggesting that irisin was able to decrease osteocyte apoptosis and cartilage degradation after ACLT [70].…”

Section: Role Of Irisin On Bone Homeostasis: In Vivo Evidencementioning

confidence: 95%

“…In addition, irisin increased phosphorylated Erk and p38 protein levels. However, in the presence of small molecule inhibitors, only ERK inhibition (PD98059; 10 µM) prevented the irisin-mediated decrease in osteocyte apoptosis, suggesting that the anti-apoptotic effects of irisin are mediated by ERK activation (Table 3) [70]. In a study by Storlino et al (2020), treatment of MLO-Y4 cells with r-irisin (100 ng/mL) for 24 h completely prevented the H 2 O 2 -induced apoptosis (Table 3) [71].…”

Section: Osteocytesmentioning

confidence: 99%

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Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Kornel

Hartogh

Klentrou

et al. 2021

IJMS

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Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.

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Section: Role Of Irisin On Bone Homeostasis: In Vivo Evidencementioning

confidence: 69%

Section: Osteocytesmentioning

confidence: 93%

Section: Role Of Irisin On Bone Homeostasis: In Vivo Evidencementioning

confidence: 95%

Section: Osteocytesmentioning

confidence: 99%

See 2 more Smart Citations

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Kornel

Hartogh

Klentrou

et al. 2021

IJMS

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“…After treatment with PDGF‐BB, the phosphorylation of p38 decreased, resulting in down‐regulation of Bax and inhibition of caspase‐3‐dependent chondrocyte apoptosis. However, the activation of Erk is believed to be a negative factor for apoptosis and has been proven to be a protective factor in the progression of OA via apoptosis and autography 28‐31 . In our research, the phosphorylation of Erk decreased after MIA treatment.…”

Section: Discussionmentioning

confidence: 43%

Recombinant platelet‐derived growth factor‐BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo

Zhu

Wang

Sun

et al. 2021

J Cellular Molecular Medi

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Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non‐pharmacological interventions, topical and oral therapies, intra‐articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet‐derived growth factor (PDGF)‐BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF‐BB at increasing concentrations. The levels of p‐p38, Bax and caspase‐3 decreased, and the level of p‐Erk increased with increasing PDGF‐BB concentration. In vivo, PDGF‐BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF‐BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up‐regulated, and the levels of collagen X and apoptosis were down‐regulated by increasing concentrations of PDGF‐BB. In conclusion, recombinant PDGF‐BB alleviated OA by down‐regulating caspase‐3‐dependent apoptosis. The effects of PDGF‐BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.

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Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

Yang

Kan

et al. 2023

Advanced Therapeutics

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Osteoclasts are cells primarily involved in bone remodeling. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration. However, given the limitations of current osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell‐free fat extract (CEFFE) is the liquid fraction obtained from adipose tissues, which are enriched with a variety of adipokines. This study aims to explore its pharmacologic effect on hyperactive osteoclastogenesis. CEFFE exhibits excellent potentials to attenuate osteoclast‐associated bone loss in ovariectomy mice and to inhibit osteoclastogenesis in primary monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE‐Cation) is identified as the main inhibitory component in osteoclast formation assay. According to liquid chromatography with tandem mass spectrometry analysis, the CEFFE‐Cation fraction mainly consists of various antioxidant enzymes and cytokines, which endow it with a superior antioxidant capacity. Meanwhile, CEFFE‐Cation is also capable of mitigating Ca2+ oscillation and subsequent nuclear factor of activated T‐cells 1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next‐generation personalized antiresorptive agent for osteolytic bone disease treatment.

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Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice

Cited by 51 publications

References 53 publications

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Recombinant platelet‐derived growth factor‐BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

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