Elsevier

Cellular Signalling

Volume 100, December 2022, 110488
Cellular Signalling

The Warburg effect in osteoporosis: Cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration

https://doi.org/10.1016/j.cellsig.2022.110488Get rights and content
Under a Creative Commons license
open access

Highlights

  • Women suffer from osteoporosis after menopause, which is characterized by a decline in the secretion of sex hormones in the later phase of life.

  • Metabolism and bone remodeling in terms of the Warburg phenomenon completely clear.

  • Osteocalcin directs ATP utilization through the sclerostin SOST gene in the bone microenvironment.

  • Selective activation of ATP production involved in osteoblast maturation could be the key strategy to fight osteoporosis.

Abstract

Osteoporosis is a silent disease of skeletal morphology that induces fragility and fracture risk in aged persons irrespective of gender. Juvenile secondary osteoporosis is rare and is influenced by familial genetic abnormalities. Despite the currently available therapeutic options, more-acute treatments are in need. Women suffer from osteoporosis after menopause, which is characterized by a decline in the secretion of sex hormones in the later phase of life. Several studies in the past two decades emphasized hormone-related pathways to combat osteoporosis. Some studies partially examined energy-related pathways, but achieving a more vivid picture of metabolism and bone remodeling in terms of the Warburg phenomenon is still warranted. Each cell requires sufficient energy for cellular propagation and growth; in particular, osteoporosis is an energy-dependent mechanism affected by a decreased cellular mass of the bone morphology. Energy utilization is the actual propagation of such diseases, and narrowing down these criteria will hopefully provide clues to formulate better therapeutic strategies. Oxidative glycolysis is a particular type of energy metabolic pathway in cancer cells that influences cellular proliferation. Therefore, the prospect of utilizing collective glucose metabolism by inducing the Warburg effect may improve cell propagation. The benefits of utilizing the energy from the Warburg effect may be a difficult task. However, it seems to improve their effectiveness in the osteoblast phenotype by connecting the selected pathways such as WNT, Notch, AKT, and Insulin signaling by targeting osteocalcin resulting in phenotypic alteration. Osteocalcin directs ATP utilization through the sclerostin SOST gene in the bone microenvironment. Thus, selective activation of ATP production involved in osteoblast maturation remains a prime strategy to fight osteoporosis.

Keywords

Glycolysis
Warburg effect
Glucose metabolism
ATP production
Osteoblast
Osteoporosis
Alternative therapy

Abbreviations

AKT
Protein kinase B
AMP
Adenosine monophosphate
AR
Androgen receptor
ATP
Adenosine triphosphate
BAD
BCL2 associated agonist of cell death
BCL2
B-cell lymphoma 2
BCL-x
B-cell lymphoma-extra large
BMPs
Bone Morphogenetic protein
ER
Endoplasmic reticulum
ERK2
Extracellular signal-regulated kinase 2
FADH
Semiquinone
FKBP12
FKBP prolyl isomerase like
GC
Glucocorticoid
Glut1
Glucose transporter 1
Glut4
Glucose transporter type 4
GTP
Guanosine triphosphate
Hex-A
Hexokinase A
Hh
Hedgehog
IGF1
Insulin-like growth factor − 1
IR
Insulin resistance
MSC
Bone marrow mesenchymal stem cells
mTOR
The mechanistic target of rapamycin
NADH
Nicotinamide adenine dinucleotide
NDP52
Nuclear domain 10 protein 52
OC
Osteocalcin
OxPhos
Oxidative phosphorylation
PI3K
phosphoinositide 3-kinase
PKC
Protein kinase C
PKM2
Pyruvate kinase isozymes M2
PPARγ
Peroxisome proliferator activated receptor-γ
PTH
Parathyroid hormone
Runx2
Runt related transcription factor – 2
S6K
Ribosomal protein S6 kinase
SGK
Serine/threonine-protein kinases
TRIM16
Tripartite motif-containing protein 16

Data availability

No data was used for the research described in the article.

Cited by (0)