title: Treatment with hydrogen sulfide attenuates sublesional skeletal deterioration following motor complete spinal cord injury in rats.
abstract: Treatment with hydrogen sulfide mitigates spinal cord injury-induced sublesional bone loss, possibly through abating oxidative stress, suppressing MMP activity, and activating Wnt/β-catenin signaling.
  
  
  
  Spinal cord injury (SCI)-induced sublesional bone loss represents the most severe osteoporosis and is resistant to available treatments to data. The present study was undertaken to explore the therapeutic potential of hydrogen sulfide (H2S) against osteoporosis in a rodent model of motor complete SCI.
  
  
  
  SCI was generated by surgical transaction of the cord at the T3-T4 levels in rats. Treatment with NaHS was initiated through intraperitoneal injection of 0.1 ml/kg/day of 0.28 mol/l NaHS from 12 h following the surgery and over 14 subsequent days.
  
  
  
  H2S levels in plasma of SCI rats were lower, which was restored by treatment with exogenous H2S. Treatment of SCI rats with exogenous H2S had no significant effect on body mass but increased bone mineral density in femurs and tibiae, increased BV/TV, Tb.Th, and Tb.N and reduced Tb.Sp in proximal tibiae, and increased mineral apposition rate (MAR), bone formation rate (BFR), and osteoblast surface and reduced eroded surface and osteoclast surface in proximal tibiae. More importantly, H2S treatment led to a significant enhancement in ultimate load, stiffness, and energy to max force of femoral diaphysis. Treatment of SCI rats with exogenous H2S reduced malondialdehyde (MDA) levels in serum and femurs, decreased hydroxyproline levels, suppressed activities of matrix metallopeptidase 9 (MMP9), and upregulated Wnt3a, Wnt6, Wnt10, and ctnnb1 expression in femurs.
  
  
  
  Treatment with H2S mitigates SCI-induced sublesional bone loss, possibly through abating oxidative stress, suppressing MMP activity, and activating Wnt/β-catenin signaling.
authors: Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Youyi East Road 555, Xi'an, 710054, China.
authors: X
authors: X
authors: Yang
authors: Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Youyi East Road 555, Xi'an, 710054, China.
authors: D
authors: D
authors: Hao
authors: Diagnostic Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, 710054, China.
authors: H
authors: H
authors: Zhang
authors: Diagnostic Center, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, 710054, China.
authors: B
authors: B
authors: Liu
authors: Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Youyi East Road 555, Xi'an, 710054, China.
authors: M
authors: M
authors: Yang
authors: Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Youyi East Road 555, Xi'an, 710054, China. hebr_hh2016@hotmail.com.
authors: B
authors: B
authors: He
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004341:Drug Evaluation; D005269:Femur / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D013904:Thoracic Vertebrae; D013977:Tibia / Q000503:physiopathology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D006862:Hydrogen Sulfide
keywords: Bone loss; Hydrogen sulfide; Oxidative stress; Spinal cord injury; Wnt/β-catenin signaling