PMID- 33352698 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20240330 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 24 DP - 2020 Dec 19 TI - Advanced Glycation End Product Inhibitor Pyridoxamine Attenuates IVD Degeneration in Type 2 Diabetic Rats. LID - 10.3390/ijms21249709 [doi] LID - 9709 AB - Type 2 diabetes mellitus (T2DM) is associated with advanced glycation end product (AGE) enrichment and considered a risk factor for intervertebral disc (IVD) degeneration. We hypothesized that systemic AGE inhibition, achieved using pyridoxamine (PM), attenuates IVD degeneration in T2DM rats. To induce IVD degeneration, lumbar disc injury or sham surgery was performed on Zucker Diabetic Sprague Dawley (ZDSD) or control Sprague Dawley (SD) rats. Post-surgery, IVD-injured ZDSD rats received daily PM dissolved in drinking water or water only. The resulting groups were SD uninjured, SD injured, ZDSD uninjured, ZDSD injured, and ZDSD injured + PM. Levels of blood glycation and disc degeneration were investigated. At week 8 post-surgery, glycated serum protein (GSP) levels were increased in ZDSDs compared to SDs. PM treatment attenuated this increase. Micro-MRI analysis demonstrated IVD dehydration in injured versus uninjured SDs and ZDSDs. In the ZDSD injured + PM group, IVD dehydration was diminished compared to ZDSD injured. AGE levels were decreased and aggrecan levels increased in ZDSD injured + PM versus ZDSD injured rats. Histological and immunohistochemical analyses further supported the beneficial effect of PM. In summary, PM attenuated GSP levels and IVD degeneration processes in ZDSD rats, demonstrating its potential to attenuate IVD degeneration in addition to managing glycemia in T2DM. FAU - Glaeser, Juliane D AU - Glaeser JD AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Ju, Derek AU - Ju D AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Tawackoli, Wafa AU - Tawackoli W AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Yang, Jae H AU - Yang JH AUID- ORCID: 0000-0001-6949-6954 AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Korea University Guro Hospital, Seoul 08308, Korea. FAU - Salehi, Khosrowdad AU - Salehi K AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Stefanovic, Tina AU - Stefanovic T AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Kanim, Linda E A AU - Kanim LEA AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Avalos, Pablo AU - Avalos P AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Kaneda, Giselle AU - Kaneda G AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Stephan, Stephen AU - Stephan S AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Metzger, Melodie F AU - Metzger MF AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - The Orthopaedic Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Bae, Hyun W AU - Bae HW AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. FAU - Sheyn, Dmitriy AU - Sheyn D AUID- ORCID: 0000-0002-3333-1485 AD - Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. AD - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. LA - eng GR - K01 AR071512/AR/NIAMS NIH HHS/United States GR - 2018 OREF Resident Clinician Scientist Training Grant/Orthopedic Research and Education Foundation/ GR - NIH/NIAMS K01AR071512/Foundation for the National Institutes of Health/ PT - Journal Article DEP - 20201219 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Blood Glucose) RN - 0 (Glycation End Products, Advanced) RN - 12001-76-2 (Vitamin B Complex) RN - 6466NM3W93 (Pyridoxamine) SB - IM MH - Animals MH - Blood Glucose MH - Diabetes Mellitus, Experimental/*complications/pathology MH - Diabetes Mellitus, Type 2/*complications/pathology MH - Diet, High-Fat/adverse effects MH - Glycation End Products, Advanced/*antagonists & inhibitors MH - Intervertebral Disc Degeneration/etiology/pathology/*prevention & control MH - Male MH - Pyridoxamine/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Rats, Zucker MH - Vitamin B Complex/*pharmacology PMC - PMC7766438 OTO - NOTNLM OT - advanced glycation end products OT - intervertebral disc degeneration OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2020/12/24 06:00 MHDA- 2021/04/02 06:00 PMCR- 2020/12/19 CRDT- 2020/12/23 01:01 PHST- 2020/11/29 00:00 [received] PHST- 2020/12/15 00:00 [revised] PHST- 2020/12/16 00:00 [accepted] PHST- 2020/12/23 01:01 [entrez] PHST- 2020/12/24 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2020/12/19 00:00 [pmc-release] AID - ijms21249709 [pii] AID - ijms-21-09709 [pii] AID - 10.3390/ijms21249709 [doi] PST - epublish SO - Int J Mol Sci. 2020 Dec 19;21(24):9709. doi: 10.3390/ijms21249709.