The Mechanism Study Of Coenzyme Q10 In Mitigating Spinal Cord Injury-induced Osteoporosis

Background and objective:Spinal cord injury(SCI)is a very serious pathological event,its serious consequences throughout the patient's life,causing pain to the family and society.SCI activates an inflammatory cascade and during this,inflammatory cells from the circulation deteriorate vital organs,including the liver,kidney and lungs.Oxidative stress and inflammation may result in post-SCI pathogenesis,including cellular apoptosis,activation of free radicals and enhanced lipid peroxidation(LPO)with subsequent depletion of anti-oxidant agents,and have a pivotal role in SCI-induced secondary organ/tissue damage.One of the imminent consequences of SCI is a significant bone loss within a few months to a few years of injury.Osteoporosis is one of the serious complications after SCI,osteoporosis has not only increased risk of fracture,but also can increase the patient's pain and dysfunction.This will undoubtedly bring more pain to patients,but also greater economic burden to the patient's family.The loss of bone mass after spinal cord injury occurred mainly in the injury site and the weight-bearing area of the extremities,such as the distal end of the femur and the proximal tibia.The damage of nerve,the further braking and the disuse of the injured limbs can lead to the bone loss,but the mechanism of osteoporosis after spinal cord injury has not been fully understood.Treatment strategies to ameliorate bone loss after SCI by physical methods include passive motion,minimal electrical stimulation and body weight-supported treadmill training.However,treatment using these strategies has no significant effects.Effective interventions may require targeting of multiple pathways to achieve significant clinical improvement after SCI,and complications including bone loss are warranted.Coenzyme Q10(Co Q10)is a key mediator of the electron transfer reaction in the respiratory chain in mitochondria.A study suggested that Co Q10 has a free-radical-quenching effect and also displays insulin-like properties in diabetic patients.Previous studies provided evidence that Co Q10 has potent anti-oxidant activity and protective efficacy in experimental SCI.Therefore,the present study was designed to investigate the mechanism of spinal cord injury induced osteoporosis and to evaluate the therapeutic efficacy of Co Q10 against bone loss induced by SCI in rats.Materials and methods:1.Mechanism study of spinal cord injury-induced osteoporosis(1)The SD rats were divided into two groups,One group was the SCI group,which resect the thoracic vertebral lamina of T10-T12 and expose the thoracic spinal cord and then spinal cord transection was performed to establish the model of completespinal cord injury.The other group was the sham operation group,which only remove the thoracic vertebral lamina of T10-T12,expose the thoracic spinal cord but no spinal cord transection.(2)The main detection means of two groups are bone mineral content(BMC)and bone mineral density(BMD)detection,systemic oxidative stress evaluation,superoxide dismutase(SOD)and malondialdehyde(MDA)level detection,inflammatory factors level of IL-6 and TNF-?detection and analysis of the determination of the skeletal gene expression of RANKL/cathepsin K and Cbfa1.(3)Conclude by analysis the data of experiments.2.Efficacy study of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis(1)The SD rats were divided into two groups,first of all,two groups resect the thoracic vertebral lamina of T10-T12 and expose the thoracic spinal cord and then spinal cord transection was performed to establish the model of complete spinal cord injury.Then the SCI group was continuously fed with saline(NS)for 10 days and the SCI+Co Q10 group was continuously fed with Co Q10 for 10 days.(2)The main detection means of two groups are bone mineral content(BMC)and bone mineral density(BMD)detection,systemic oxidative stress evaluation,superoxide dismutase(SOD)and malondialdehyde(MDA)level detection,inflammatory factors level of IL-6 and TNF-? detection and analysis of the determination of the skeletal gene expression of RANKL/cathepsin K and Cbfa1.(3)Conclude by analysis the data of experiments.Results:1.Mechanism study of spinal cord injury-induced osteoporosis We successfully constructed spinal cord injury model by vertebral resection.BMD and BMC values of SCI rats are decreased,assessment of systemic oxidative stress improving,SOD soaring,SCI rats displayed a signifcant elevation of serum inflammatory cytokines IL-6 and TNF-? and the level of MDA.The m RNA levels of osteoclast-specifc genes RANKL and cathepsin K were increased in femurs of SCI rats.Then,the m RNA levels of the osteoblast-specifc gene Cbfa1 were decreased in femurs of SCI rats.2.Efficacy study of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis Co Q10 was administered via gavage daily for 10 days in SCI+Co Q10 group.We discovered that Co Q10 alleviates decreased BMD and BMC in rats following SC,oxidative stress in bones and SOD decreasing.Co Q10 reduces serum inflammatory markers and MDA in SCI rats.Of note,treatment with Co Q10 signifcantly decreased the RANKL and cathepsin K m RNA levels in femurs.Conclusions:1.Oxidative stress may be related to the pathogenesis of osteoporosis induced by spinal cord injury.2.Coenzyme Q10 mitigates spinal cord injury-induced osteoporosis.