eCM (Eur Cell Mater / e Cells & Materials) eCM Open Access Scientific Journal
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2013   Volume No 25 – pages 268-283

Title: Mechanism of parathyroid hormone-mediated suppression of calcification markers in human intervertebral disc cells

Author: P Madiraju, R Gawri, H Wang, J Antoniou, F Mwale

Address: Lady Davis Institute for Medical Research, Room 602, 3755 Cote Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada

E-mail: fmwale at ldi.jgh.mcgill.ca

Key Words: Parathyroid hormone; intervertebral disc degeneration; disc calcification; type X collagen; type II collagen; gene expression; mitogen-activated protein kinase.

Publication date: May 2nd 2013

Abstract: In degenerative intervertebral discs (IVD), type X collagen (COL X) expression (associated with hypertrophic differentiation) and calcification has been demonstrated. Suppression of COL X expression and calcification during disc degeneration can be therapeutic. In the present study we investigated the potential of human parathyroid hormone 1-34 (PTH) in suppressing indicators of calcification potential (alkaline phosphatase (ALP), Ca2+, inorganic phosphate (Pi)), and COL X expression. Further, we sought to elucidate the mechanism of PTH action in annulus fibrosus (AF) and nucleus pulposus (NP) cells from human lumbar IVDs with moderate to advanced degeneration. Mitogen activated protein kinase (MAPK) signalling and alterations in the markers of calcification potential were analysed. PTH increased type II collagen (COL II) expression in AF (~200 %) and NP cells (~163 %) and decreased COL X levels both in AF and NP cells (~75 %). These changes in the expression of collagens were preceded by MAPK phosphorylation, which was increased in both AF and NP cells by PTH after 30 min. MAPK signalling inhibitor U0126 and protein kinase-A inhibitor H-89 DCH attenuated PTH stimulated COL II expression in both cell types. PTH decreased ALP activity and increased Ca2+ release only in NP cells. The present study demonstrates that PTH can potentially retard IVD degeneration by stimulating matrix synthesis and suppressing markers of calcification potential in degenerated disc cells via both MAPK and PKA signalling pathways. Inhibition of further mineral deposition may therefore be a viable therapeutic option for improving the status of degenerating discs.

Article download: Pages 268-283 (PDF file)
DOI: 10.22203/eCM.v025a19