TY - JOUR T1 - Meta-analysis Reveals Genetic Correlates of Osteoporosis Pathogenesis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.200951 SP - jrheum.200951 AU - Laith K. Hasan AU - Jihad Aljabban AU - Michael Rohr AU - Mohamed Mukhtar AU - Nikhil Adapa AU - Rahaf Salim AU - Nabeal Aljabban AU - Saad Syed AU - Sharjeel Syed AU - Maryam Panahiazar AU - Dexter Hadley AU - Wael Jarjour Y1 - 2020/12/01 UR - http://www.jrheum.org/content/early/2020/11/26/jrheum.200951.abstract N2 - Objective Osteoporosis is a growing health care burden. By identifying osteoporosis promoting genetic variations, we can spotlight targets for new pharmacologic therapies that will improve patient outcomes. In this meta-analysis, we analyzed mesenchymal stem cell biomarkers in patients with osteoporosis. Methods We employed our Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis to define osteoporosis pathogenesis. We compared 15 osteoporotic and 14 healthy control mesenchymal stem cell (MSC) samples. We then analyzed the genetic signature in Ingenuity Pathway Analysis. Results The top canonical pathways identified which were statistically significant included the SPINK1 Pancreatic Cancer Pathway, Calcium Signaling, Pancreatic Adenocarcinoma Signaling, Axonal Guidance Signaling and Glutamate Receptor Signaling. Upstream regulators involved in this disease process included ESR1, dexamethasone, CTNNB1, CREB1, ERBB2. Conclusion Although there has been extensive research looking at the genetic basis for inflammatory arthritis, very little literature exists currently that has identified genetic pathways contributing to osteoporosis. Our study has identified several important genes involved in osteoporosis pathogenesis including ESR1, CTNNB1, CREB1 and ERBB2. ESR1 has been shown to have numerous polymorphisms, which may play a prominent role in osteoporosis. The Wnt pathway, which includes the CTNNB1 gene identified in our study, plays a prominent role in bone mass regulation. Wnt pathway polymorphisms can increase susceptibility to osteoporosis. Our analysis also suggests a potential mechanism for ERBB2 in osteoporosis through Semaphorin 4D (SEMA4D). Our meta-analysis identifies several genes and pathways that can be targeted to develop new anabolic drugs for osteoporosis treatment. ER -