title: Nucleus pulposus cells derived IGF-1 and MCP-1 enhance osteoclastogenesis and vertebrae disruption in lumbar disc herniation.
abstract: METHODS
  Chronic strained lumbar disc herniation (LDH) cases were classified into bulging LDH, herniated LDH and prolapse LDH types according to imaging examination, and vertebrae disruptions were evaluated. Cytokines derived from the nucleus pulposus cells were detected, and their effects on osteoclastogenesis, as well as the mechanisms involved, were studied via an in vitro osteoclast differentiation system.
  
  
  OBJECTIVE
  To clarify the mechanisms of lumbar vertebrae resorption induced by lumbar herniation.
  
  
  BACKGROUND
  Chronic strained lumbar disc herniation induced vertebrae erosion exacerbates quality of patients' life and clinical outcome. Although nucleus pulposus cells derived cytokines were reported to play an important role in this pathogenesis, the fundamental mechanisms underlying this process are still unclear.
  
  
  METHODS
  Chronic strained lumbar disc herniation patients were diagnosed with CT scan and T2-weighted magnetic resonance imaging. RNA was extracted from 192 surgical specimens of the herniated lumbar disc and 29 surgical excisions of the lumbar disc from spinal injury patients. The expressions of osteoclastogenesis related cytokines and chemokines were examined using real time PCR. Monocytes were induced into osteoclast with M-CSF and RANKL in vitro, while the IGF-1 and MCP-1 were added into the differentiation procedure in order to evaluate the effects and explore the molecular mechanisms.
  
  
  RESULTS
  Vertebrae erosion had a positive relationship with lumbar disc herniation severity types. In all of the osteoclastogenesis related cytokines, the IGF-1 and MCP-1 were the most highly expressed in the nucleus pulposus cells. IGF-1 enhances activation of NF-kB signaling directly, but MCP-1 upregulated the expression of RANK, so that enhanced cellular sensitivity to RANKL resulted in increasing osteoclastogenesis and activity.
  
  
  CONCLUSIONS
  Lumbar herniation induced overexpression of IGF-1 and MCP-1 in nucleus pulposus cells aggravated vertebral erosions. Hence, this study suggests that targeting osteoclastogenesis related cytokines has potential clinical significance in the treatment of lumbar disc herniation patients.
authors: Department of Orthopedics, Tenzhou Central People's Hosipital Tenzhou 277500, Shandong, China ; Department of Orthopedics, Shandong University Qilu Hospital Jinan, Shandong, 250012, China.
authors: Zhongjiao
authors: Z
authors: Zhu
authors: Department of Emergency, Tengzhou Hospital of Traditional Chinese Medicine Tengzhou 277500, Shandong, China.
authors: Peng
authors: P
authors: Huang
authors: Department of Orthopedics, Tenzhou Central People's Hosipital Tenzhou 277500, Shandong, China.
authors: Yanxue
authors: Y
authors: Chong
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center Houston 77054, Texas, USA.
authors: Suraj K
authors: SK
authors: George
authors: Department of Orthopedics, Tenzhou Central People's Hosipital Tenzhou 277500, Shandong, China.
authors: Bingtao
authors: B
authors: Wen
authors: Department of Orthopedics, Peking University People's Hospital Beijing 100029, China.
authors: Na
authors: N
authors: Han
authors: Division of Medicine, Center for Cancer Immunology Research, The University of Texas M D Anderson Cancer Center Houston 77054, Texas USA.
authors: Zhiqiang
authors: Z
authors: Liu
authors: Department of Orthopedics, Tenzhou Central People's Hosipital Tenzhou 277500, Shandong, China.
authors: Lixin
authors: L
authors: Kang
authors: Department of Orthopedics, Shandong University Qilu Hospital Jinan, Shandong, 250012, China.
authors: Nie
authors: N
authors: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000150:complications* / Q000473:pathology; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007334:Insulin-Like Growth Factor I
keywords: IGF-1; Lumbar disc herniation; MCP-1; osteoclast; vertebra disruption