Osteoporosis and autophagy: What is the relationship?

Florencio‐Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Simões, Manuel de Jesus; Simões, Ricardo Santos; Baracat, Maria Cândida Pinheiro; Sasso-Cerri, Estela; Cerri, Paulo Sérgio

doi:10.1590/1806-9282.63.02.173

Cited by 41 publications

(40 citation statements)

References 92 publications

(113 reference statements)

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“…Osteoblasts and osteocytes produce OPG (osteoprotegerin), a decoy receptor for RANKL, which binds to the cytokine and prevents its interaction with RANK, interrupting osteoclastogenesis [ 24 ].…”

Section: Bone Remodelingmentioning

confidence: 99%

“…This phase allows the acidification and degradation of the delivered macromolecules into amino acids, lipids, nucleotides, and energy for further use by the cell [ 46 ]. Several proteins are involved like dynein, which regulates vesicular transport, Rab7, Beclin-1, SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors), and many others that facilitate autophagosome maturation [ 24 , 25 ]. Some proteins such as p62, NBR1 (neighbor of BRCA1 gene), and ALFY (autophagy-linked FYVE protein) are located at the autophagosome surface and sequester the degradation targets [ 25 ].…”

Section: Autophagy and Bone Remodelingmentioning

confidence: 99%

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The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

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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.

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Section: Bone Remodelingmentioning

confidence: 99%

Section: Autophagy and Bone Remodelingmentioning

confidence: 99%

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

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“…In recent years, studies have shown that autophagy plays important roles for the maintenance of bone homeostasis, and its dysregulation has been related to bone loss and osteoporosis [18], [14][15][16][17]. It has been demonstrated that suppression of ATG7 (autophagy related 7), an essential gene for autophagy, in mice osteocytes promotes a marked increase in oxidative stress and bone loss [18].…”

Section: Introductionmentioning

confidence: 99%

Effects of estrogen status in osteocyte autophagy and its relation to osteocyte viability in alveolar process of ovariectomized rats

Florencio‐Silva

Sasso

Sasso-Cerri

et al. 2018

Biomedicine & Pharmacotherapy

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Estrogen maintains osteocyte viability, whereas its deficiency induces osteocyte apoptosis. As autophagy is important for osteocyte viability, we hypothesized whether the anti-apoptotic effect of estrogen is related to autophagy in osteocytes. Thirty adult female rats were sham-operated (SHAM) or ovariectomized (OVX). After three weeks, twelve rats of SHAM and OVX groups were killed before treatment (basal period), whereas the remaining rats received estrogen (OVXE) or vehicle (OVX) for 45 days. Fragments of maxilla containing alveolar process of the first molars were embedded in paraffin or Araldite. Paraffin-sections were stained with hematoxylin/eosin for histomorphometry, or subjected to the silver impregnation method for morphological analysis of osteocyte cytoplasmic processes. Autophagy was analyzed by immunohistochemical detections of beclin-1, MAP-LC3α and p62, whereas apoptosis was evaluated by immunohistochemical detections of cleaved caspase-3 and BAX, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method and by ultrastructural analysis. Araldite-semithin sections were subjected to the Sudan-black method for detection of lipids. OVX-basal group showed high frequency of caspase-3-, TUNEL- and p62-positive osteocytes accompanied with low frequency of beclin-1- and MAP-LC3α-positive osteocytes. At 45 days, OVXE group exhibited higher number of osteocytes, higher frequency of beclin-1- and MAP-LC3α-positive osteocytes, and lower frequency of caspase-3, BAX-, TUNEL- and p62-positive osteocytes than OVX group. Significant reduction in bone area was observed in the OVX compared to OVXE and SHAM groups. The highest frequency of Sudan-Black-positive osteocytes and osteocytes with scarce cytoplasmic processes, or showing apoptotic features were mainly observed in OVX groups. Our results indicate that estrogen deficiency decreases autophagy and increases apoptosis, whereas estrogen replacement enhances osteocyte viability by inhibiting apoptosis and maintaining autophagy in alveolar process osteocytes. These results suggest that the anti-apoptotic effect of estrogen may be, at least in part, related to autophagy regulation in osteocytes.

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“…These dysfunctional mitochondria accumulate in the cells due to defective clearance as a result of downregulated autophagy, so they continue to produce higher levels of superoxide anion that leak from them and attack other cellular components eventually leading to irreversible cellular damage and death . In addition, mitochondrial superoxide produced by SOD2 loss promotes the upregulation of the RANKL expression associated with a higher rate of bone resorption in mice .…”

Section: Discussionmentioning

confidence: 99%

Autophagy in osteoporosis: Relation to oxidative stress

Ezzat

Louka

Zakaria

et al. 2018

J of Cellular Biochemistry

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Impaired autophagy and oxidative stress are implicated in the development of many diseases. This study aimed to investigate the involvement of autophagy represented by autophagy-related gene 7 (Atg7) and oxidative stress represented by superoxide dismutase 2 (SOD2) gene expression and enzyme activity in the pathogenesis of osteoporosis. Atg7 and SOD2 gene relative expression were evaluated by SYBR green quantitative real-time-polymerase chain reaction in the osteoporotic group (n = 26) versus the osteoporosis free group (n = 14). SOD2 enzyme activity was evaluated by colorimetric method in both study groups. Both Atg7 and SOD2 relative expression showed highly significant decrease (P < 0.01) between both groups. However, SOD2 enzyme activity showed no significant difference between the two groups. There was a significant direct correlation between Atg7 and SOD2 gene expression in both study groups. Atg7 relative expression showed significant ( P < 0.01) direct correlation with vitamin D serum levels and body mass index in osteoporotic group. In conclusion, both genes are involved in the pathogenesis of osteoporosis and this could be amenable to future therapeutic intervention.

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Osteoporosis and autophagy: What is the relationship?

Cited by 41 publications

References 92 publications

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

Effects of estrogen status in osteocyte autophagy and its relation to osteocyte viability in alveolar process of ovariectomized rats

Autophagy in osteoporosis: Relation to oxidative stress

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