Fabrizio Russo1, Luca Ambrosio1, Kevin Ngo2, Gianluca Vadalà1, Vincenzo Denaro1, Yong Fan3, Gwendolyn Sowa4, James D Kang5, Nam Vo2. 1. Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Rome, Italy. 2. Ferguson Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. 3. Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA. 4. Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Cancer, University of Pittsburgh, Pittsburgh, PA. 5. Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract
STUDY DESIGN: An experimental laboratory study. OBJECTIVE: To investigate the pathogenesis of intervertebral disc degeneration (IDD) in a murine model of type 1 diabetes mellitus (DM), namely nonobese diabetic (NOD) mouse. SUMMARY OF BACKGROUND DATA: IDD is a leading contributor of low back pain, which represents one of the most disabling symptoms within the adult population. DM is a chronic metabolic disease currently affecting one in 10 adults in the United States. It is associated with an increased risk of developing IDD, but the underlying process remains poorly understood. METHODS: Total disc glycosaminoglycan content, proteoglycan synthesis, aggrecan fragmentation, glucose transporter gene expression, and apoptosis were assessed in NOD mice and wild-type euglycemic control mice. Spinal structural and molecular changes were analyzed by micro-computed tomography, histological staining (Safranin-O and fast green), and quantitative immunofluorescence (anti-ADAMTS-4 and -5 antibodies). RESULTS: Compared with euglycemic controls, NOD mice showed increased disc apoptosis and matrix aggrecan fragmentation. Disc glycosaminoglycan content and histological features of NOD mice did not significantly differ from those of euglycemic littermates. CONCLUSION: These data demonstrate that DM may contribute to IDD by increasing aggrecan degradation and promoting cell apoptosis, which may represent early indicators of the involvement of DM in the pathogenesis of IDD. LEVEL OF EVIDENCE: N/A.
STUDY DESIGN: An experimental laboratory study. OBJECTIVE: To investigate the pathogenesis of intervertebral disc degeneration (IDD) in a murine model of type 1 diabetes mellitus (DM), namely nonobese diabetic (NOD) mouse. SUMMARY OF BACKGROUND DATA: IDD is a leading contributor of low back pain, which represents one of the most disabling symptoms within the adult population. DM is a chronic metabolic disease currently affecting one in 10 adults in the United States. It is associated with an increased risk of developing IDD, but the underlying process remains poorly understood. METHODS: Total disc glycosaminoglycan content, proteoglycan synthesis, aggrecan fragmentation, glucose transporter gene expression, and apoptosis were assessed in NOD mice and wild-type euglycemic control mice. Spinal structural and molecular changes were analyzed by micro-computed tomography, histological staining (Safranin-O and fast green), and quantitative immunofluorescence (anti-ADAMTS-4 and -5 antibodies). RESULTS: Compared with euglycemic controls, NOD mice showed increased disc apoptosis and matrix aggrecan fragmentation. Disc glycosaminoglycan content and histological features of NOD mice did not significantly differ from those of euglycemic littermates. CONCLUSION: These data demonstrate that DM may contribute to IDD by increasing aggrecan degradation and promoting cell apoptosis, which may represent early indicators of the involvement of DM in the pathogenesis of IDD. LEVEL OF EVIDENCE: N/A.
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