4.6 Article

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

Journal

CELLULAR SIGNALLING
Volume 100, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2022.110488

Keywords

Glycolysis; Warburg effect; Glucose metabolism; ATP production; Osteoblast; Osteoporosis; Alternative therapy

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Osteoporosis is a common disease in elderly people and currently lacks effective treatment options. Women after menopause are particularly prone to osteoporosis, and hormone-related pathways are considered important in combating the disease. Energy metabolism plays a key role in the development of osteoporosis, and understanding the energy pathways associated with the disease can provide clues for the development of treatment strategies.
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 oste-oporosis 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.

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