title: ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.
abstract: Cross-sectional cohort analysis of patients with Modic Changes (MC).
  
  
  
  Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications.
  
  
  
  MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown.
  
  
  
  Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels.
  
  
  
  Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs.
  
  
  
  Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA. dudli@panamerica.ch.
authors.forename: Stefan
authors.identifier: 0000-0001-7351-713X
authors.initials: S
authors.lastname: Dudli
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Sing
authors.affiliation: Stanford Spine Clinic, Stanford University Medical Center, Stanford, USA.
authors.forename: Serena S
authors.initials: SS
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Sigurd H
authors.initials: SH
authors.lastname: Berven
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Burch
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Vedat
authors.initials: V
authors.lastname: Deviren
authors.affiliation: Stanford Spine Clinic, Stanford University Medical Center, Stanford, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Bobby K B
authors.initials: BKB
authors.lastname: Tay
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Todd F
authors.initials: TF
authors.lastname: Alamin
authors.affiliation: Stanford Spine Clinic, Stanford University Medical Center, Stanford, USA.
authors.forename: Ma Agnes Martinez
authors.initials: MAM
authors.lastname: Ith
authors.affiliation: Division of Hematology, University of Colorado Denver, Denver, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Pietras
authors.affiliation: Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lotz
mesh_terms: D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis; D015854:Up-Regulation
keywords: Bone marrow; Cross-talk; Fibrosis; Inflammation; Modic change; Myelopoiesis; Neurotrophic; Osteoclastogenesis; Pain; Pathobiology