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2017 ; 7
(ä): 45623
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Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of
the Notochordal Cell-Rich Nucleus Pulposus
#MMPMID28358123
Matta A
; Karim MZ
; Isenman DE
; Erwin WM
Sci Rep
2017[Mar]; 7
(ä): 45623
PMID28358123
show ga
Degenerative disc disease (DDD) is associated with spinal pain often leading to
long-term disability. However, the non-chondrodystrophic canine intervertebral
disc is protected from the development of DDD, ostensibly due to its retention of
notochordal cells (NC) in the nucleus pulposus (NP). In this study, we
hypothesized that secretome analysis of the NC-rich NP will lead to the
identification of key proteins that delay the onset of DDD. Using
mass-spectrometry, we identified 303 proteins including components of TGF?- and
Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth
in the bioactive fractions of serum free, notochordal cell derived conditioned
medium (NCCM). Ingenuity Pathway Analysis revealed TGF?1 and CTGF as major hubs
in protein interaction networks. In vitro treatment with TGF?1 and CTGF promoted
the synthesis of healthy extra-cellular matrix proteins, increased cell
proliferation and reduced cell death in human degenerative disc NP cells. A
single intra-discal injection of recombinant TGF?1 and CTGF proteins in a
pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In
conclusion, we demonstrate the potential of TGF?1 and CTGF to mitigate the
progression of disc degeneration and the potential use of these molecules in a
molecular therapy to treat the degenerative disc.