Metabolic consideration of epiphyseal growth: Survival responses in a taxing environment

Shapiro, Irving M.; Srinivas, Vickram

doi:10.1016/j.bone.2006.09.030

Cited by 23 publications

(13 citation statements)

References 29 publications

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“…Autophagy was also detected in growth plate, epiphyseal fusion, and osteoarthritis (Shapiro et al, 2008;van den Berg, 2011). Chondrocytes in these areas were under hypoxia, which mediated the evaluation of HIF1a expression, reduced mTOR activities, and then initiated autophagy (Bohensky et al, 2007;Shapiro and Srinivas, 2007). Under these circumstances, autophagy degraded harmful cytosol and organelles to promote the cell survival.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Prior to Chondrocyte Cell Death During the Degeneration of Meckel's Cartilage

Yang

Zhang

Liu

et al. 2012

The Anatomical Record

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The central portion of Meckel's cartilage degenerates almost immediately after birth. Whether autophagy is involved in this process remains unclear. Thus, to explore the role of autophagy during this process, we have detected the expression of autophagy and apoptosis-related markers in embryonic mice. In E15, Beclin1 and LC3 expressions were weak and negative in Meckel's cartilage, respectively. In E16, chondrocytes of the central portion became hypertrophic. Moderate immunoreactivities of Beclin1 and LC3 were observed in prehypertrophic and hypertrophic chondrocytes of the central portion. In E17, the degradation occurred in the central portion and expanded anteriorly and posteriorly. Beclin1 expression was observed in Meckel's cartilage with an increase in the hypertrophic chondrocytes of the central portion. The expression of LC3 was detected specifically in terminally differentiated hypertrophic chondrocytes. The mRNA expressions of LC3 and Beclin1 from E15 to E17 significantly increased. This result is in accord with the histologic findings. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay and Caspase 3 expression demonstrated that apoptosis was detected in the lateral part of terminal hypertrophic chondrocytes along the degeneration area of Meckel's cartilage. In addition, Bcl2 expression increased significantly from E15 to E17. These results indicate that autophagy is involved in hypertrophic chondrocytes during the degradation of Meckel's cartilage and occurs prior to chondrocyte cell death during this process. Anat Rec,

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Section: Discussionmentioning

confidence: 99%

Autophagy Prior to Chondrocyte Cell Death During the Degeneration of Meckel's Cartilage

Yang

Zhang

Liu

et al. 2012

The Anatomical Record

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“…To test whether HIF-1␣ stabilization is essential in mediating the metabolic effects of BGP, we silenced HIF-1␣ using siRNA. Because HIF-1 is recognized as a chondrogenesis survival factor, 21,24 we refrained from blocking its activity during the long-term differentiation schedule and used the short-term model. Although treatment with purified BGP resulted in elevation of HIF-1␣ protein and mRNA within 5 to 10 minutes, silencing of HIF-1␣ counteracted this effect in both ATDC5 and MOVAS cells ( Figure 6A, B, C).…”

Section: Bgp Upregulates Genes Of Glucose Transport and Utilization Vmentioning

confidence: 99%

“…21 Therefore, BGP-induced elevation of PFK and PDK1 enzyme levels indicates metabolic conversion to the glycolytic breakdown of glucose. Concomitant with increased glycolysis, we also demonstrated that BGP inhibits the opposite process of gluconeogenesis, by decreasing the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase enzymes.…”

Section: Idelevich Et Al Bgp Increases Hif-1␣-dependent Metabolism E67mentioning

confidence: 99%

“…Residing chondrocytes progress from proliferative layer to postmitotic hypertrophic stage and, in addition to acquiring a unique phenotype, change their energy status from oxidative metabolism to anaerobic glycolysis. 21 One mechanism by which chondrocytes sense and metabolically adapt to low O 2 tension is via stabilization of hypoxia-inducible factor 1 (HIF-1), which is a heterodimer of two proteins, HIF-1␣ and HIF-1␤. 22 Under normoxia, HIF-1␣ is hydroxylated and rapidly degraded by the proteasome.…”

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confidence: 99%

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Bone Gla Protein Increases HIF-1α–Dependent Glucose Metabolism and Induces Cartilage and Vascular Calcification

Idelevich

Rais

Monsonego-Ornan

2011

ATVB

115

106

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“…A number of workers have shown that the oxygen tension in the cartilage is low, and hence chondrocytes generate much of their metabolic energy through anaerobic glycolysis (Shapiro et al, 2005). We have argued that the environment may also activate an autophagic response in the maturing cells, which serves to maintain chondrocyte viability until the induction of the apoptosis (Shapiro and Srinivas, 2007). It is now evident that the autophagic response is seen in many cell types and serves a physiologic role in generating energy utilizing the cells’ own protein and lipid stores (Klionsky, 2005).…”

Section: Introductionmentioning

confidence: 99%

Autophagy: A New Phase in the Maturation of Growth Plate Chondrocytes Is Regulated by HIF, mTOR and AMP Kinase

Srinivas

Bohensky

Shapiro³

2008

Cells Tissues Organs

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The overall goal of the investigation was to examine autophagy in the growth plate and to ascertain how this process was regulated. Herein, we show that in the postmitotic maturing zone of the growth plate, chondrocytes express an autophagic phenotype. This robust and particulate immunohistochemical response provides direct evidence that autophagy is a new and transient stage in the chondrocyte maturation pathway. We found that induction of autophagy was regulated by mTOR, a sensor of cellular metabolism. When mTOR was inhibited, changes in LC3 fluorescence indicated that this kinase regulated development of the autophagic state. To determine if AMP kinase was required for chondrocyte autophagy, we suppressed its expression in N1511 cells using siRNA technology. When these cells were serum starved, a condition that triggers autophagy, there was no change in LC3 distribution. This result confirmed that AMP kinase was required for the induction of the autophagic response. Based on the 2 studies described above, and our previous observation that HIF-1 is required for the induction of autophagy, we put forward the hypothesis that autophagy is regulated by the activities of AMP kinase and mTOR in a HIF-1-dependent manner. Once autophagy is activated, the postmitotic chondrocytes would be expected to remain viable in their unique microenvironment and complete their life cycle.

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Metabolic consideration of epiphyseal growth: Survival responses in a taxing environment

Cited by 23 publications

References 29 publications

Autophagy Prior to Chondrocyte Cell Death During the Degeneration of Meckel's Cartilage

Autophagy Prior to Chondrocyte Cell Death During the Degeneration of Meckel's Cartilage

Bone Gla Protein Increases HIF-1α–Dependent Glucose Metabolism and Induces Cartilage and Vascular Calcification

Autophagy: A New Phase in the Maturation of Growth Plate Chondrocytes Is Regulated by HIF, mTOR and AMP Kinase

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