PURPOSE: Intervertebral disc degeneration related to postmenopausal osteoporosis is an important issue in spinal disorder research. This study aimed to investigate the effects of salmon calcitonin (sCT), as an antiresorptive medication, on lumbar intervertebral disc degeneration using a rat ovariectomy (OVX) model. METHODS: Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: the sham-operated (Sham) group and two ovariectomized groups treated with vehicle (OVX+V) or sCT (OVX+CT; 16 IU/kg, sc) on alternate days for 6 months. Treatment began after OVX and continued for 6 months. At the end of the experiment, bone mineral density (BMD), micro-CT analysis, biomechanical testing, histology, and immunohistochemistry were performed for all groups. RESULTS: Salmon calcitonin significantly maintained vertebrae BMD, percent bone volume, and biomechanical strength, when compared with the OVX+V group. The changes of mucoid degeneration in the nucleus pulposus and calcification in the middle cartilage endplate were more moderate in the OVX+CT group compared with the OVX+V group, and immunohistochemistry revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 expressions in the OVX+CT group. CONCLUSIONS: Salmon calcitonin treatment was effective in delaying the process of the disc degeneration in OVX rats. The underlying mechanisms may be related to preservation of structural integrity and function of vertebrae, and affecting extracellular matrix metabolism by modulating the expressions of MMPs, aggrecan and type II collagen to protect the disc from degeneration.
PURPOSE:Intervertebral disc degeneration related to postmenopausal osteoporosis is an important issue in spinal disorder research. This study aimed to investigate the effects of salmon calcitonin (sCT), as an antiresorptive medication, on lumbar intervertebral disc degeneration using a rat ovariectomy (OVX) model. METHODS: Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: the sham-operated (Sham) group and two ovariectomized groups treated with vehicle (OVX+V) or sCT (OVX+CT; 16 IU/kg, sc) on alternate days for 6 months. Treatment began after OVX and continued for 6 months. At the end of the experiment, bone mineral density (BMD), micro-CT analysis, biomechanical testing, histology, and immunohistochemistry were performed for all groups. RESULTS: Salmon calcitonin significantly maintained vertebrae BMD, percent bone volume, and biomechanical strength, when compared with the OVX+V group. The changes of mucoid degeneration in the nucleus pulposus and calcification in the middle cartilage endplate were more moderate in the OVX+CT group compared with the OVX+V group, and immunohistochemistry revealed a significant increase in aggrecan and type II collagen expressions, but marked reductions in matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 expressions in the OVX+CT group. CONCLUSIONS: Salmon calcitonin treatment was effective in delaying the process of the disc degeneration in OVX rats. The underlying mechanisms may be related to preservation of structural integrity and function of vertebrae, and affecting extracellular matrix metabolism by modulating the expressions of MMPs, aggrecan and type II collagen to protect the disc from degeneration.
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Authors: Alon Lai; Jennifer Gansau; Sarah E Gullbrand; James Crowley; Carla Cunha; Stefan Dudli; Julie B Engiles; Marion Fusellier; Raquel M Goncalves; Daisuke Nakashima; Jeffrey Okewunmi; Matthew Pelletier; Steven M Presciutti; Jordy Schol; Yoshiki Takeoka; Sidong Yang; Takashi Yurube; Yejia Zhang; James C Iatridis Journal: JOR Spine Date: 2021-05-26