MACF1 overexpression in BMSCs alleviates senile osteoporosis in mice through TCF4/miR-335–5p signaling pathway

Zhang, Kewen; Qiu, Wuxia; Li, Hui; Li, Jun; Wang, Pai; Chen, Zhihao; Lin, Xiuping; Qian, Airong

doi:10.1016/j.jot.2023.02.003

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…34 Elevated levels of miR-335 in MSCs induces cellular aging, as indicated by heightened SA-β-gal function, elevated p16 protein levels, reduced cell multiplication, and compromised immunoregulatory and maturation potential. 35 Our prior research has demonstrated that blocking miR-873-5p yields cardioprotective effects by promoting AMPK activation in cardiomyocytes via XIAP targeting. 15 Additionally, our current study reveals significantly elevated levels of miR-873-5p in human adipose-derived MSCs (AMSCs) and serum from aged donors.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Diminishment of miR-543 and miR-590-3p impairs MSCs’ ability to differentiate into adipogenic and clonogenic cells, leading to the senescence phenotype . Elevated levels of miR-335 in MSCs induces cellular aging, as indicated by heightened SA-β-gal function, elevated p16 protein levels, reduced cell multiplication, and compromised immunoregulatory and maturation potential . Our prior research has demonstrated that blocking miR-873-5p yields cardioprotective effects by promoting AMPK activation in cardiomyocytes via XIAP targeting .…”

Section: Discussionmentioning

confidence: 99%

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miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction

Zhu,

Du,

Duan

et al. 2024

ACS Pharmacol. Transl. Sci.

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Aging poses obstacles to the functionality of human mesenchymal stem cells (MSCs), resulting in a notable decline in their valuable contribution to myocardial infarction (MI). MicroRNAs (miRNAs) play a pivotal role in governing MSC aging; nonetheless, the specific mechanisms remain puzzling. This research delved into the value of miR-873-5p in the management of MSC aging and investigated whether the restraint of miR-873-5p could regenerate aged MSCs (AMSCs), thereby enhancing their healing success for MI. In this study, MSCs were isolated from both young donors (referred to as YMSCs) and aged donors (referred to as AMSCs). The senescence status of these MSCs was evaluated through the application of age-related β-galactosidase (SA-β-gal) staining. Following this assessment, the MSCs, including those treated with anti-miR-873-5p-AMSCs, were then transplanted into the hearts of Sprague−Dawley rats experiencing acute myocardial infarction. Increasing miR-873-5p levels in YMSCs resulted in elevated cellular aging, whereas reducing miR-873-5p expression decreased aging in AMSCs. Mechanistically, miR-873-5p inhibited autophagy in MSCs through the AMPK signaling pathway, leading to cellular aging by suppressing the Cab39 expression. Partial alleviation of these effects was achieved by the administration of the autophagy inhibitor 3-methyladenine. Grafting of anti-miR-873-5p-AMSCs, by enhancing angiogenesis and bolstering cell survival, led to an improvement in cardiac function in the rat model, unlike the transplantation of AMSCs. miR-873-5p which serves as a pivotal element in mediating MSC aging through its regulation of the Cab39/AMPK signaling pathway. It represents an innovative target for revitalizing AMSCs and enhancing their heart-protective abilities.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction

Zhu,

Du,

Duan

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…The expression of RUNX2 indicates the onset of osteogenic differentiation, which occurs at the earliest stage of bone formation (35). The expression of RUNX2 in bone tissue after OVX remains controversial, and may be affected by different stages of osseointegration, mouse background or various bone tissue (36)(37)(38). OCN is a non-collagen protein that is present in bone tissue, and levels are indicative of maturity during osteogenic differentiation (39).…”

Section: Discussionmentioning

confidence: 99%

gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice

Zhang,

Zhao

et al. 2024

Mol Med Rep

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C1q/tumor necrosis factor-related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)-induced mice via the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3-E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro-computed tomography scans and bone-related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate-resistant acid phosphatase (TRAP) staining. Runt-related transcription factor-2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C-telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N-terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3-E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription-quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX-induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3-E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3-E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX-induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.

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“… 431 , 432 Moreover, we demonstrated MACF1, the activator of Wnt/β-catenin signaling, as a promotor for osteoblast differentiation and bone formation 125 , 126 , 276 and a novel potential therapeutic target for treating osteoporosis. 433 Overexpression of MACF1 specifically in mesenchymal stem cells prevented aging-induced osteoporosis in 18- and 21-month-old mice. 433 …”

Section: Targeting Wnt Signaling In Bone Disease Treatmentmentioning

confidence: 98%

“… 433 Overexpression of MACF1 specifically in mesenchymal stem cells prevented aging-induced osteoporosis in 18- and 21-month-old mice. 433 …”

Section: Targeting Wnt Signaling In Bone Disease Treatmentmentioning

confidence: 98%

Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease

Hu,

Chen,

Qian

et al. 2024

Bone Res

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Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies.

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MACF1 overexpression in BMSCs alleviates senile osteoporosis in mice through TCF4/miR-335–5p signaling pathway

Cited by 9 publications

References 42 publications

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction

gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice

Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease

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