Genetic Basis Associated with Osteoporosis: An in-vivo Study

Abstract

Osteoporosis is a very common disease that affects the bones and is characterized by decreased bone mineral density, as a result of impaired bone mineralization. Consequently, patients suffering from osteoporosis are highly prone to fractures, which sometimes can be life-threatening. Usually, patients suffering from osteoporosis have no symptoms until the first fracture occurs. Osteoporosis is primarily diagnosed by low Bone Mineral Density (BMD), which is assessed using DEXA scan. Besides bisphosphonates, which are used as the first line of treatment for osteoporosis, Selective Estrogen Receptor Modulators (SERMs) are also commonly used. Lately, studying the pathogenesis of osteoporosis on the molecular level has gained more attention. Several miRNAs, genes and epigenetic modifications have been linked to osteoporosis. This allows for better understanding of the disease incidence, progression, and treatment. The main aim of this work is to study the molecular mechanisms fundamental for the progression and treatment of osteoporosis. Using bone samples from established osteoporotic rat models, we investigated the role of WNT-signalling pathway in osteoporosis development and treatment, in addition to the role of histone acetylation and miR-148a-3p in progression and treatment of the disease. Our study suggests that WNT-signalling pathway is inhibited during the progression of osteoporosis; and that upon treatment, WNT-signalling recovers to close-to-normal levels. Our work also indicates that the extent of histone acetylation of WNT-1 gene, and the level of miR- 148a-3p, could be involved in the regulation of WNT-signalling pathway during the progression and treatment of osteoporosis. Taken together, our results show that targeting WNT-signalling pathway for the development of future treatments for osteoporosis seems to be a realistic option.