PMID- 31463436
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231013
IS  - 2572-1143 (Electronic)
IS  - 2572-1143 (Linking)
VI  - 1
IP  - 1
DP  - 2018 Mar
TI  - Degenerate intervertebral disc-like pH induces a catabolic mechanoresponse in 
      human nucleus pulposus cells.
PG  - e1004
LID - 10.1002/jsp2.1004 [doi]
LID - e1004
AB  - Mechanical stimulation is known to influence intervertebral disc (IVD) cell 
      behavior and function, but the effect on disc cells is routinely considered in 
      isolation from other microenvironmental factors. Acidic pH has been shown to be a 
      prominent and detrimental microenvironmental factor present in degenerate IVDs, 
      but its influence on the human disc cell mechanoresponse has never been studied. 
      We investigated the response of agarose-encapsulated human nucleus pulposus (NP) 
      cells to 0.004 MPa, 1.0 Hz and 1 hour of compression (Flexcell FX4000 Compression 
      System) under pH conditions representative of nondegenerate (pH 7.1) and 
      degenerate (pH 6.5) IVDs. Cell viability, extracellular matrix production, and 
      expression of anabolic/anti-catabolic and catabolic genes were assessed. We 
      report that preculture of NP cells in agarose gels was required in order for 
      cells to be mechanoresponsive, and this correlated with increased type VI 
      collagen, alpha5beta1 integrin, and fibronectin expression. Furthermore, the matrix 
      homeostatic response observed at pH 7.1 (representative of nondegenerate IVDs; 
      increased aggrecan [AGC], tissue inhibitor of metalloproteinases-1 [TIMP1], 
      matrix metalloproteinase-3 [MMP3], a disintegrin and metalloproteinase with 
      thrombospondin motif-5 [ADAMTS5] gene expression) was RGD-integrin dependent, 
      whereas only MMP3 remained mechanoresponsive at pH 6.5, and this was independent 
      of RGD-integrins. Our findings suggest differential mechanotransduction pathways 
      operating for specific genes, with RGD-integrin dependent AGC expression, but not 
      RGD-independent MMP3 expression, inhibited at pH representative of degenerate 
      IVDs (pH 6.5), which could contribute to the catabolic phenotype observed during 
      IVD degeneration. CLINICAL SIGNIFICANCE: Characterizing the influence of the 
      mechanical and chemical intervertebral disc microenvironment on disc cells, 
      particularly in disc degeneration, could help develop future therapeutic 
      strategies for the treatment of discogenic back pain.
FAU - Hodson, Nathan W
AU  - Hodson NW
AD  - Division of Cell Matrix Biology and Regenerative Medicine, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health University of Manchester 
      Manchester UK.
FAU - Patel, Sonal
AU  - Patel S
AD  - Division of Cell Matrix Biology and Regenerative Medicine, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health University of Manchester 
      Manchester UK.
FAU - Richardson, Stephen M
AU  - Richardson SM
AUID- ORCID: 0000-0002-7637-4135
AD  - Division of Cell Matrix Biology and Regenerative Medicine, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health University of Manchester 
      Manchester UK.
FAU - Hoyland, Judith A
AU  - Hoyland JA
AUID- ORCID: 0000-0003-4876-5208
AD  - Division of Cell Matrix Biology and Regenerative Medicine, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health University of Manchester 
      Manchester UK.
AD  - NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS 
      Foundation Trust Manchester Academic Health Science Centre Manchester UK.
FAU - Gilbert, Hamish T J
AU  - Gilbert HTJ
AUID- ORCID: 0000-0003-2571-765X
AD  - Division of Cell Matrix Biology and Regenerative Medicine, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health University of Manchester 
      Manchester UK.
AD  - Wellcome Trust Centre for Cell-Matrix Research, Division of Cell Matrix Biology 
      and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, 
      Medicine and Health University of Manchester Manchester UK.
LA  - eng
GR  - 19884/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
DEP - 20180311
PL  - United States
TA  - JOR Spine
JT  - JOR spine
JID - 101722350
PMC - PMC6711490
OTO - NOTNLM
OT  - acidic pH
OT  - intervertebral disc degeneration
OT  - mechanical load
OT  - mechanotransduction
OT  - nucleus pulposus
COIS- The authors declare no conflict of interests.
EDAT- 2018/03/11 00:00
MHDA- 2018/03/11 00:01
PMCR- 2018/03/11
CRDT- 2019/08/30 06:00
PHST- 2017/11/23 00:00 [received]
PHST- 2018/01/22 00:00 [revised]
PHST- 2018/02/12 00:00 [accepted]
PHST- 2019/08/30 06:00 [entrez]
PHST- 2018/03/11 00:00 [pubmed]
PHST- 2018/03/11 00:01 [medline]
PHST- 2018/03/11 00:00 [pmc-release]
AID - JSP21004 [pii]
AID - 10.1002/jsp2.1004 [doi]
PST - epublish
SO  - JOR Spine. 2018 Mar 11;1(1):e1004. doi: 10.1002/jsp2.1004. eCollection 2018 Mar.