Bone Cell Autophagy Is Regulated by Environmental Factors

Zahm, Adam M.; Bohensky, Jolene; Adams, Christopher S.; Shapiro, Irving M.; Srinivas, Vickram

doi:10.1159/000324647

Cited by 50 publications

(58 citation statements)

References 13 publications

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“…However, particulate LC3 fluorescence has not been observed in bone-lining cells or osteoblasts. Furthermore, autophagic osteocytes were primarily observed residing at a distance from the haversian canal2324. Our study found the expression of LC3 in osteoblasts which indicated that osteoblasts may undergo autophagy at bone fracture sites.…”

Section: Discussionsupporting

confidence: 51%

Acidic pH environment induces autophagy in osteoblasts

Zhang

Lai

et al. 2017

Sci Rep

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Osteoblasts (OBs) play an important role in bone fracture healing, yet the extreme adverse microenvironment in fracture sites has a negative impact on the survival of OBs. Therefore, it is important to study how OBs behave in the complex fracture microenvironment. Studies have shown that autophagy plays a pivotal role in maintaining cellular homeostasis and defending the cell against adverse microenvironments. In this study we found the induction of autophagy in OBs at femoral bone fracture sites, which may be a result of ischemia, oxidative stress and hypoxia within the local area. At fracture sites a low pH environment also developed. Until now it has been unclear whether the induction of autophagy in osteoblasts is triggered by the acidic pH environment. Therefore, we cultured OBs in vitro in media of different pH values, and found both autophagy and apoptosis increased in OBs in acidic conditions. However, when autophagy inhibitor chloroquine (CQ) was used, apoptosis increased significantly compared with that without CQ. Thus indicating that inhibition of autophagy may promote apoptosis in OBs in an acidic environment, which may provide a new therapeutic strategy to decrease cell apoptosis in OBs through the use of drugs that modulate the autophagic state.

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Section: Discussionsupporting

confidence: 51%

Acidic pH environment induces autophagy in osteoblasts

Zhang

Lai

et al. 2017

Sci Rep

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“…30 Autophagy was first shown to be a major survival mechanism of the long-lived osteocytes in stressful environments. 31,32,33 Recent work by Onal M. et al reports that autophagy suppression in osteocytes results in a reduced bone volume of 6-mo-old mice associated with an overall reduction in OB and OC numbers. 34 The study of Whitehouse et al, 35 then demonstrates that genetic truncation of the selective autophagic receptor Nbr1 in a murine model leads to increased osteoblast differentiation and activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

Autophagy in osteoblasts is involved in mineralization and bone homeostasis

et al. 2014

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Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies.

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“…59 In fact, the expression of LC3 in osteocytes is greater than in osteoblasts. 61 Osteocytes are long-lived cells located in gaps delimited by mineralized bone matrix and, consequently, are positioned in an environment more susceptible to hypoxia and to the accumulation of oxidative stress. 55 It is believed that under these conditions autophagy plays an important role in the survival of osteocytes.…”

Section: Role Of Autophagy In Bone Biologymentioning

confidence: 99%

“…Non-functional mitochondria response to calcium-mediated stress, a hypoxia-inducing transcription factor (HIF-1) positively regulates autophagy, indicating that low oxygen tension serves as a regulator of autophagy in this type of cell. 61 Low-dose glucocorticoid treatment has also been shown to induce autophagy in osteocytes in response to increased oxidative stress caused by treatment, preserving the viability of these cells. [62][63][64] Studies indicate that autophagy also plays an important role in bone resorption by osteoclasts.…”

Section: Role Of Autophagy In Bone Biologymentioning

confidence: 99%

Osteoporosis and autophagy: What is the relationship?

Florencio‐Silva

Sasso

Simões

et al. 2017

Rev. Assoc. Med. Bras.

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Autophagy is a survival pathway wherein non-functional proteins and organelles are degraded in lysosomes for recycling and energy production. Therefore, autophagy is fundamental for the maintenance of cell viability, acting as a quality control process that prevents the accumulation of unnecessary structures and oxidative stress. Increasing evidence has shown that autophagy dysfunction is related to several pathologies including neurodegenerative diseases and cancer. Moreover, recent studies have shown that autophagy plays an important role for the maintenance of bone homeostasis. For instance, in vitro and animal and human studies indicate that autophagy dysfunction in bone cells is associated with the onset of bone diseases such as osteoporosis. This review had the purpose of discussing the issue to confirm whether a relationship between autophagy dysfunction and osteoporosis exits.

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Bone Cell Autophagy Is Regulated by Environmental Factors

Cited by 50 publications

References 13 publications

Acidic pH environment induces autophagy in osteoblasts

Acidic pH environment induces autophagy in osteoblasts

Autophagy in osteoblasts is involved in mineralization and bone homeostasis

Osteoporosis and autophagy: What is the relationship?

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