Metaanalysis Reveals Genetic Correlates of Osteoporosis Pathogenesis.

Laith K Hasan, Jihad Aljabban, Michael Rohr, Mohamed Mukhtar, Nikhil Adapa, Rahaf Salim, Nabeal Aljabban, Saad Syed, Sharjeel Syed, Maryam Panahiazar, Dexter Hadley, Wael Jarjour

Journal: The Journal of rheumatology 2021;48(6):940-945

PMID: 33262303

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Abstract

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 , dexamethasone, , and .

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 , and has been shown to have numerous polymorphisms, which may play a prominent role in osteoporosis. The Wnt pathway, which includes the 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 in osteoporosis through Semaphorin 4D (). Our metaanalysis identifies several genes and pathways that can be targeted to develop new anabolic drugs for osteoporosis treatment.

Address: L.K. Hasan, BBA, Tulane University School of Medicine, New Orleans, Lousiana; [email protected].; J. Aljabban, MD, MMSc, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.; M. Rohr, BS, D. Hadley, MD, PhD, University of Central Florida College of Medicine, Orlando, Florida.; M. Mukhtar, BS, Michigan State University College of Medicine, Lansing, Michigan.; N. Adapa, MD, State University of New York Upstate Medical University, Syracuse, New York.; R. Salim, BS, Case Western University, Cleveland, Ohio.; N. Aljabban, BS, Penn State College of Medicine, Hershey, Pennsylvania.; S. Syed, BS, S. Syed, MD, Stanford University School of Medicine, Palo Alto, California.; M. Panahiazar, PhD, University of California San Francisco, San Francisco, California.; W. Jarjour, MD, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

DOI: 10.3899/jrheum.200951

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/osteoporosis.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-1745

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-ERBB2-3

MeSH Terms: Bone Density, Cyclic AMP Response Element-Binding Protein, Estrogen Receptor alpha, Humans, Mesenchymal Stem Cells, Osteoporosis, Receptor, ErbB-2, Wnt Signaling Pathway, beta Catenin