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Aging Dis. 2019 Jun 1;10(3):483-496. doi: 10.14336/AD.2018.0616. eCollection 2019 Jun.

Adipose-derived Stem Cells Attenuates Diabetic Osteoarthritis via Inhibition of Glycation-mediated Inflammatory Cascade.

Author information

1
1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
2
2Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
3
3School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
4
4School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
5
5Wake Forest Institute of Regenerative Medicine, Winston-Salem, NC, USA.
6
6Department of Periodontics, College of Dental Medicine, Columbia University, New York, USA.
7
7Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan.
8
8Stem Cell Research Center, Cosmetic Clinic Group, Taipei, Taiwan.
9
9Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan.
10
10Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.

Abstract

Diabetes mellitus (DM) is well-known to exert complications such as retinopathy, cardiomyopathy and neuropathy. However, in recent years, an elevated osteoarthritis (OA) complaints among diabetics have been observed, portending the risk of diabetic OA. Since formation of advanced glycation end products (AGE) is believed to be the etiology of various diseases under hyperglycemic conditions, we firstly established that streptozotocin-induced DM could potentiate the development of OA in C57BL/6J mouse model, and further explored the intra-articularly administered adipose-derived stem cell (ADSC) therapy focusing on underlying AGE-associated mechanism. Our results demonstrated that hyperglycemic mice exhibited OA-like structural impairments including a proteoglycan loss and articular cartilage fibrillations in knee joint. Highly expressed levels of carboxymethyl lysine (CML), an AGE and their receptors (RAGE), which are hallmarks of hyperglycemic microenvironment were manifested. The elevated oxidative stress in diabetic OA knee-joint was revealed through increased levels of malondialdehyde (MDA). Further, oxidative stress-activated nuclear factor kappa B (NF-κB), the marker of proinflammatory signalling pathway was also accrued; and levels of matrix metalloproteinase-1 and 13 were upregulated. However, ADSC treatment attenuated all OA-like changes by 4 weeks, and dampened levels of CML, RAGE, MDA, NF-κB, MMP-1 and 13. These results suggest that during repair and regeneration, ADSCs inhibited glycation-mediated inflammatory cascade and rejuvenated cartilaginous tissue, thereby promoting knee-joint integrity in diabetic milieu.

KEYWORDS:

Diabetes mellitus; adipose-derived stem cells; advanced glycation end product; articular cartilage; osteoarthritis; proteoglycans

Conflict of interest statement

Disclosure of Conflicts of Interest Authors declare no conflict of interests.

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