Estrogen enhances human osteoblast survival and function via promotion of autophagy

Gavali, Shubhangi; Gupta, Manoj Kumar; Daswani, Bhavna; Wani, Mohan R.; Sirdeshmukh, Ravi; Khatkhatay, M. Ikram

doi:10.1016/j.bbamcr.2019.06.014

Cited by 52 publications

(40 citation statements)

References 36 publications

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“…In postmenopausal osteoporosis, estrogen therapy effectively prevents bone loss ( 39 ). Emerging evidence has demonstrated that estrogen exhibits an inhibitory role in osteoclast formation and enhances osteoblast function ( 40 , 41 ). During estrogen-decreased osteoclast differentiation, miR-27a remarkably enhances the inhibitory effect of estrogen ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

Liu

Zhu

et al. 2020

Mol Med Rep

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osteoporosis is a complex multifactorial disorder characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures or broken bones. Balanced bone remodeling is tightly regulated by the differentiation, activity and apoptosis of bone-forming osteoblasts and bone-resorbing osteoclasts. Micrornas (mirs) are dysregulated in osteoporosis, but whether they control osteogenic differentiation and skeletal biology, or could serve as therapeutic targets remains to be elucidated. The present study identified miR-27a-3p as a critical suppressor of osteoblastogenesis. Bioinformatics analysis and luciferase reporter assays demonstrated that miR-27a-3p directly targeted and controlled the expression of osterix (osx), an early response gene essential for bone formation, through its 3'-untranslated region. miR-27a-3p functionally inhibited the differentiation of preosteoblasts by decreasing osx expression, which synergistically contributed to bone formation. miR-27a-3p level was significantly decreased during osteogenic differentiation and increased in the serum of patients with osteoporosis. Together, miR-27a-3p contributed to diminished osteogenic function during osteogenic differentiation and might thus serve as a therapeutic target and diagnostic biomarker for osteoporosis.

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Section: Discussionmentioning

confidence: 99%

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

Liu

Zhu

et al. 2020

Mol Med Rep

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“…In addition, the study found that when human primary MSCs differentiated into OB, RAB3GAP1 was downregulated during osteoblast differentiation, and autophagic flux decreased. However, estrogen upregulates transcription and protein levels and promotes autophagy in undifferentiated MSCs and RAB3GAP1 cells that are differentiating (Gavali et al, 2019). After direct administration of 17β‐estradiol in OCPs and OVX mice, the results showed that 17β‐estradiol enhanced the autophagic response of OCPs and inhibited the antiosteoclastogenic effect of OCPs (Cheng et al, 2020).…”

Section: Therapeutic Potential Of Autophagy In Bone Diseasementioning

confidence: 99%

The role of autophagy in bone homeostasis

Guo

Yang

et al. 2021

Journal Cellular Physiology

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Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.

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“…Reactive oxygen species (ROS) can induce autophagy and this leads to both non-apoptotic cell death and cell survival [70]. Autophagy might be a mechanism of cell survival [71]. Three types of autophagy have been reported: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA) [72].…”

Section: Cross Talk Between Egfr Signaling and Autophagymentioning

confidence: 99%

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

Kwon

Kim

Jung

et al. 2019

Cancers

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Epidermal growth factor receptor (EGFR) plays critical roles in cell proliferation, tumorigenesis, and anti-cancer drug resistance. Overexpression and somatic mutations of EGFR result in enhanced cancer cell survival. Therefore, EGFR can be a target for the development of anti-cancer therapy. Patients with cancers, including non-small cell lung cancers (NSCLC), have been shown to response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR antibodies. However, resistance to these anti-EGFR treatments has developed. Autophagy has emerged as a potential mechanism involved in the acquired resistance to anti-EGFR treatments. Anti-EGFR treatments can induce autophagy and result in resistance to anti-EGFR treatments. Autophagy is a programmed catabolic process stimulated by various stimuli. It promotes cellular survival under these stress conditions. Under normal conditions, EGFR-activated phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling inhibits autophagy while EGFR/rat sarcoma viral oncogene homolog (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) signaling promotes autophagy. Thus, targeting autophagy may overcome resistance to anti-EGFR treatments. Inhibitors targeting autophagy and EGFR signaling have been under development. In this review, we discuss crosstalk between EGFR signaling and autophagy. We also assess whether autophagy inhibition, along with anti-EGFR treatments, might represent a promising approach to overcome resistance to anti-EGFR treatments in various cancers. In addition, we discuss new developments concerning anti-autophagy therapeutics for overcoming resistance to anti-EGFR treatments in various cancers.

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Estrogen enhances human osteoblast survival and function via promotion of autophagy

Cited by 52 publications

References 36 publications

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

The role of autophagy in bone homeostasis

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments

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