title: Identification of cell surface-specific markers to target human nucleus pulposus cells: expression of carbonic anhydrase XII varies with age and degeneration.
abstract: OBJECTIVE
  Back pain is a major cause of disability, affecting millions of people worldwide. One cause of axial back pain is degeneration of the nucleus pulposus (NP) of the intervertebral disc. This study was undertaken to investigate associations of NP cells with cell surface-specific proteins that differ from proteins in closely related cell types, i.e., intervertebral disc anulus fibrosus (AF) cells and articular cartilage (AC) chondrocytes, in order to identify potential surface molecules for directed delivery of therapeutic agents.
  
  
  METHODS
  We conducted a complementary DNA microarray analysis of 16 human samples from 6 donors, followed by gene list reduction using a systematic approach. Genes that were more highly expressed in NP than AC cells, contained transmembrane domains, and appeared attractive for targeting were assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). As a viable candidate, carbonic anhydrase XII (CAXII) was analyzed at the protein level by immunohistochemistry and functional study.
  
  
  RESULTS
  Microarray results demonstrated a clear divide between the AC and AF and between the AC and NP samples. However, the transcriptomic profile of AF and NP samples displayed a greater intersubject similarity. Of the 552 genes with up-regulated expression in NP cells, 90 contained transmembrane domains, and 28 were quantified by RT-PCR. Most intense CAXII labeling was observed in the NP of discs from young subjects and in degenerative tissue.
  
  
  CONCLUSIONS
  CAXII may be considered for detection or targeting of degenerating disc cells. Furthermore, CAXII may be involved in pH regulation of NP cells. Its potential for directed delivery of regenerative factors and its functional role in NP cell homeostasis warrant further investigation.
authors: University College Dublin, Dublin, Ireland.
authors: Karen A
authors: KA
authors: Power
authors: Sibylle
authors: S
authors: Grad
authors: Joost P H J
authors: JP
authors: Rutges
authors: Laura B
authors: LB
authors: Creemers
authors: Mattie H P
authors: MH
authors: van Rijen
authors: Peadar
authors: P
authors: O'Gaora
authors: J Gerard
authors: JG
authors: Wall
authors: Mauro
authors: M
authors: Alini
authors: Abhay
authors: A
authors: Pandit
authors: William M
authors: WM
authors: Gallagher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D015415:Biomarkers / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII