RT Journal Article SR Electronic T1 Metaanalysis Reveals Genetic Correlates of Osteoporosis Pathogenesis JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 940 OP 945 DO 10.3899/jrheum.200951 VO 48 IS 6 A1 Laith K. Hasan A1 Jihad Aljabban A1 Michael Rohr A1 Mohamed Mukhtar A1 Nikhil Adapa A1 Rahaf Salim A1 Nabeal Aljabban A1 Saad Syed A1 Sharjeel Syed A1 Maryam Panahiazar A1 Dexter Hadley A1 Wael Jarjour YR 2021 UL http://www.jrheum.org/content/48/6/940.abstract AB Objective. Osteoporosis is a growing healthcare burden. By identifying osteoporosis-promoting genetic variations, we can spotlight targets for new pharmacologic therapies that will improve patient outcomes. In this metaanalysis, we analyzed mesenchymal stem cell (MSC) biomarkers in patients with osteoporosis.Methods. We employed our Search Tag Analyze Resource for the Gene Expression Omnibus (STARGEO) platform to conduct a metaanalysis to define osteoporosis pathogenesis. We compared 15 osteoporotic and 14 healthy control MSC samples. We then analyzed the genetic signature in Ingenuity Pathway Analysis.Results. The top canonical pathways identified that were statistically significant included the serine peptidase inhibitor kazal type 1 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, CTNNβ1, CREB1, and ERBB2.Conclusion. Although there has been extensive research looking at the genetic basis for inflammatory arthritis, very little literature currently exists that has identified genetic pathways contributing to osteoporosis. Our study has identified several important genes involved in osteoporosis pathogenesis including ESR1, CTNNβ1, 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 CTNNβ1 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 metaanalysis identifies several genes and pathways that can be targeted to develop new anabolic drugs for osteoporosis treatment.