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

Chithravel Vadivalagan; Anand Krishnan; Siang-Jyun Chen; You-Cheng Hseu; Sathish Muthu; Rajib Dhar; Alaa A A Aljabali; Murtaza M Tambuwala

doi:10.1016/j.cellsig.2022.110488

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

Cell Signal. 2022 Dec:100:110488. doi: 10.1016/j.cellsig.2022.110488. Epub 2022 Oct 5.

Authors

Chithravel Vadivalagan¹, Anand Krishnan², Siang-Jyun Chen³, You-Cheng Hseu⁴, Sathish Muthu⁵, Rajib Dhar⁶, Alaa A A Aljabali⁷, Murtaza M Tambuwala⁸

Affiliations

¹ Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan. Electronic address: marinedrug.9@gmail.com.
² Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa. Electronic address: krishnana@ufs.ac.za.
³ Institute of Nutrition, College of Health Care, China Medical University, Taichung, 406040, Taiwan.
⁴ Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, 41354, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan. Electronic address: ychseu@mail.cmu.edu.tw.
⁵ Department of Orthopaedics, Government Medical College and Hospital, Dindigul-624003, Tamil Nadu, India.
⁶ Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, -603203, Tamilnadu, India.
⁷ Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, 21163, Jordan.
⁸ Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK. Electronic address: m.tambuwala@lincoln.ac.uk.

PMID: 36208706
DOI: 10.1016/j.cellsig.2022.110488

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

Publication types

Review