Aberrant Expression of <em>COX-2</em> and <em>FOXG1</em> in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors
Benjamen T. O’Donnell,
Tia A. Monjure,
Sara Al-Ghadban,
Clara J. Ives,
Michael P. L’Ecuyer,
Claire Rhee,
Monica Romero-Lopez,
Zhong Li,
Stuart B. Goodman,
Hang Lin,
Rocky S. Tuan,
Bruce A. Bunnell
Affiliations
Benjamen T. O’Donnell
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Tia A. Monjure
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Sara Al-Ghadban
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Clara J. Ives
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Michael P. L’Ecuyer
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Claire Rhee
Departments of Orthopaedic Surgery and Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
Monica Romero-Lopez
Departments of Orthopaedic Surgery and Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
Zhong Li
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Stuart B. Goodman
Departments of Orthopaedic Surgery and Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA
Hang Lin
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Rocky S. Tuan
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Bruce A. Bunnell
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
Osteoarthritis (OA) is a degenerative joint disease resulting in limited mobility and severe disability. Type II diabetes mellitus (T2D) is a weight-independent risk factor for OA, but a link between the two diseases has not been elucidated. Adipose stem cells (ASCs) isolated from the infrapatellar fat pad (IPFP) may be a viable regenerative cell for OA treatment. This study analyzed the expression profiles of inflammatory and adipokine-related genes in IPFP-ASCs of non-diabetic (Non-T2D), pre-diabetic (Pre-T2D), and T2D donors. Pre-T2D ASCs exhibited a substantial decrease in levels of mesenchymal markers CD90 and CD105 with no change in adipogenic differentiation compared to Non-T2D and T2D IPFP-ASCs. In addition, Cyclooxygenase-2 (COX-2), Forkhead box G1 (FOXG1) expression and prostaglandin E2 (PGE2) secretion were significantly increased in Pre-T2D IPFP-ASCs upon stimulation by interleukin-1 beta (IL-1β). Interestingly, M1 macrophages exhibited a significant reduction in expression of pro-inflammatory markers TNFα and IL-6 when co-cultured with Pre-T2D IPFP-ASCs. These data suggest that the heightened systemic inflammation associated with untreated T2D may prime the IPFP-ASCs to exhibit enhanced anti-inflammatory characteristics via suppressing the IL-6/COX-2 signaling pathway. In addition, the elevated production of PGE2 by the Pre-T2D IPFP-ASCs may also suggest the contribution of pre-diabetic conditions to the onset and progression of OA.
