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

被引:26
作者
Dubey, Navneet Kumar [1 ,2 ]
Wei, Hong-Jian [2 ,3 ,4 ]
Yu, Sung-Hsun [2 ]
Williams, David F. [5 ]
Wang, Joseph R. [6 ]
Deng, Yue-Hua [7 ]
Tsai, Feng-Chou [8 ]
Wang, Peter D. [4 ,9 ]
Deng, Win-Ping [2 ,4 ,10 ]
机构
[1] Taipei Med Univ, Coll Biomed Engn, Grad Inst Biomed Mat & Tissue Engn, Taipei, Taiwan
[2] Taipei Med Univ, Coll Oral Med, Stem Cell Res Ctr, Taipei, Taiwan
[3] Taipei Med Univ, Coll Oral Med, Sch Dent Technol, Taipei, Taiwan
[4] Taipei Med Univ, Coll Oral Med, Sch Dent, Taipei, Taiwan
[5] Wake Forest Inst Regenerat Med, Winston Salem, NC USA
[6] Columbia Univ, Coll Dent Med, Dept Periodont, New York, NY USA
[7] Fu Jen Catholic Univ, Dept Life Sci, New Taipei, Taiwan
[8] Cosmet Clin Grp, Stem Cell Res Ctr, Taipei, Taiwan
[9] Taipei Med Univ Hosp, Dept Dent, Taipei, Taiwan
[10] Fu Jen Catholic Univ, Grad Inst Basic Med, New Taipei, Taiwan
关键词
Diabetes mellitus; osteoarthritis; articular cartilage; proteoglycans; advanced glycation end product; adipose-derived stem cells; KAPPA-B ACTIVATION; END-PRODUCTS; MATRIX METALLOPROTEINASES; OXIDATIVE STRESS; STROMAL CELLS; EXPRESSION; CARTILAGE; RECEPTOR; INDUCE; CHONDROCYTES;
D O I
10.14336/AD.2018.0616
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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-articularh 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-kappa B), 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-kappa B, 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.
引用
收藏
页码:483 / 496
页数:14
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