MRI, hematoxylin-eosin staining, or Collagen-II immunochemistry were performed to observe intervertebral disk degeneration in conditional miR-155 overexpression mice and miR-155 knockout mice.
TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model.
In summary, this study demonstrates that LIF plays a role in promoting ECM synthesis in the degenerated NP cells as a protective role in intervertebral disc degeneration (IDD), which is related to the activation of ERK1/2 signaling pathway.
Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo.
Treatment with Sparstolonin B significantly suppressed toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor (NF)‑κB protein expression, inhibited NAPDH oxidase 2 protein expression and induced phosphoinositide 3‑kinase and phosphorylated protein kinase B protein expression in the IVDD rat model.
There is a large and growing body of evidence that many members of MMPs and ADAMTSs are highly expressed in degenerative IVD tissue and cells, and are closely involved in ECM breakdown and the process of disc degeneration.
The aim of the study was to assess if nerve growth factor (NGF) might alter gene expression of IVD cells and contribute to disc degeneration by enhancing expression or activity of factors that cause breakdown of IVD matrix.
Mouse spines were graded for key histological features of disc degeneration in all the time points and expression of two key FOXO downstream targets, sestrin 3 (SESN3) and superoxide dismutase (SOD2), was assessed by immunohistochemistry.
PHD3<sup>-/-</sup> mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A. PHD3 silencing decreased hypoxic activation of HIF-1α C-terminal transactivation domain (C-TAD), but not HIF-1α-N-terminal-(N)-TAD or HIF-2α-TAD.
Histological examinations and aggrecan, Col1A1, Col2A1 and matrix metalloprotease (MMP)-3 mRNA expression confirmed the disc degeneration, supporting the imaging results.