Treatment with resveratrol attenuates sublesional bone loss in spinal cord‐injured rats

Abstract

BACKGROUND AND PURPOSESublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of the present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal cord-injured rats. EXPERIMENTAL APPROACHComplete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400 mg·kg −1 body mass per day −1 , intragastrically) was initiated 12 h after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI. KEY RESULTSTreatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral total sulfhydryl content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the up-regulation of mRNA levels of PPARγ, adipose-specific fatty-acid-binding protein and lipoprotein lipase, and restored mRNA levels of Wnt1, low-density lipoprotein-related protein 5, Axin2, ctnnb1, insulin-like growth factor 1 (IGF-1) and receptor for IGF-1 in femurs and tibiae. CONCLUSIONS AND IMPLICATIONSTreatment with RES attenuated sublesional bone loss in spinal-cord-injured rats, associated with abating oxidative stress, attenuating inflammation, depressing PPARγ signalling, and restoring Wnt/β-catenin and IGF-1 signalling.Abbreviations 25(OH)D, 25-hydroxyvitamin D; aP2, adipose-specific fatty-acid-binding protein; BFR/BS, bone formation rate/bone surface; BMD, bone mineral density; BV/TV, trabecular bone volume fraction; DPD, deoxypyridinoline; ES/BS, eroded surface/bone surface; IGF-1, insulin-like growth factor 1; IGF-1R, receptor for insulin-like growth factor; IGFBP5, insulin-like growth-factor-binding-protein 5; LPL, lipoprotein lipase; Lrp5, low-density lipoprotein-related protein 5; MAR, mineral apposition rate; MDA, malondialdehyde; Oc.S/BS, osteoclast surface/bone

CSF Proteomics of Secondary Phase Spinal Cord Injury in Human Subjects: Perturbed Molecular Pathways Post Injury

“…SCI typically throws the normal functioning of Central Nervous System (CNS) and adjoining tissues into a haywire, as is evident from our study and several others [3] , [4] , [22] – [29] , [36] . Two perspectives emerge in this scenario: the off-balance situation of the CNS pathophysiology and the start and progression of efforts to bring back homeostasis and repair.…”

“…Iron homeostasis [28] and blood coagulation pathways are also active during this phase. Administration of Resveratrol in SCI rats has shown upregulation of IGF-1 and Wnt1 mRNA indicating the involvement of insulin receptor signalling and Wnt pathways in post SCI pathophysiology [29] . tRNA transcription, which is a perturbed pathway in our study, probably points towards increased protein synthesis and has not been reported so far.…”

Resveratrol neuroprotection in stroke and traumatic CNS injury

“…Resveratrol treatment was shown to decrease edema and inflammatory cytokine release (specifically IL-1β, IL-10, TNFα, and myeloperoxidase) after SCI in rats (Liu et al, 2011). Clinical studies showed that SCI patients suffer sub-lesion bone loss (Kocina, 1997), and resveratrol treatment prevents IL-6 and MDA levels leading to increased genesis of osteoblasts and osteoclasts in an experimental rat model of SCI (Wang et al, 2013). …”

Cilostazol Attenuates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclastogenesis

“…The beneficial effect of cAMP on bone has been suggested by the findings in several systems [ 2 , 21 – 24 ]. Resveratrol which acts as a PDE inhibitor to activate cAMP signaling improves age-related metabolic syndromes [ 21 ] while it attenuates bone loss in vivo [ 22 , 23 ]. Most cannabinoid receptor antagonists activate cAMP production and mice with type 1 cannabinoid receptor deficiency exhibit increased peak bone mass due to reduced bone resorption [ 24 ].…”