Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs.
OBJECTIVE
Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with alpha5beta1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.


METHODS
Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the alpha5beta1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real-time quantitative polymerase chain reaction.


RESULTS
Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the alpha5beta1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.


CONCLUSIONS
Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the alpha5beta1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.
Le Maitre
Christine Lyn
CL
Sheffield Hallam University, Sheffield, UK.
Frain
Jennie
J
Millward-Sadler
Jane
J
Fotheringham
Andrew P
AP
Freemont
Anthony John
AJ
Hoyland
Judith Alison
JA
D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D016474:Weight-Bearing; D055815:Young Adult
D053674:Aggrecans; D000970:Antineoplastic Agents; D039081:Integrin alpha5beta1; D016023:Integrins; D009842:Oligopeptides; D012333:RNA, Messenger; C047981:arginyl-glycyl-aspartic acid