Targeting autophagy in osteoporosis: From pathophysiology to potential therapy

Xu, Li; Xu, Jiankun; Dai, Bingyang; Wang, Xinluan; Guo, Quanyi; Qin, Ling

doi:10.1016/j.arr.2020.101098

Cited by 73 publications

(79 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study we focused on the potential roles of ER stress, UPR and autophagy in SARS-CoV-2 infection because such fundamental cellular processes have been shown to contribute to the pathophysiology of other diseases [44–47]. Also, in case of viral infections, the role of ER during viral replication is well-documented, and the activation of UPR has been reported in other coronaviruses-infected cells [48–51].…”

Section: Discussionmentioning

confidence: 99%

Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules

Balakrishnan

Lai

2021

Preprint

View full text Add to dashboard Cite

Coronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2α arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2α and autophagy expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules

Balakrishnan

Lai

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Autophagy plays a dual role in regulating osteoclasts. Even if autophagy is important for bone resorption, autophagy activation does not necessarily stimulate osteoclast activity ( 84 ). OPG activates the AMPK protein, resulting in the inactivation of mammalian target of rapamycin complex 1 (mTORC1).…”

Section: Phenotypic Changes In Osteoclasts During the Development Of Osteoporosis Based On Energy Metabolismmentioning

confidence: 99%

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Lin

Zhu

2021

Front. Endocrinol.

View full text Add to dashboard Cite

In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.

show abstract

“…Autophagy plays dual roles in the regulation of osteoclasts. Even if autophagy is important for the bone resorption, it does not mean that its activation necessarily stimulates osteoclast activity [ 91 ]. OPG inhibits osteoclast differentiation and activity, and also influences the autophagy pathway upregulating the expression of Atg5, 7, 12, 13, Beclin-1, and LC3I/II ratio in bone marrow macrophages [ 92 ].…”

Section: Autophagy In Osteoclast Differentiation/functionmentioning

confidence: 99%

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

View full text Add to dashboard Cite

Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.

show abstract

Targeting autophagy in osteoporosis: From pathophysiology to potential therapy

Cited by 73 publications

References 193 publications

Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules

Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

Contact Info

Product

Resources

About