03/11/2023
Low-grade inflammation 🔥 in intervertebral disc degeneration.
👉Degeneration of intervertebral disc (IVD) is weakly associated with long term pain and disability outcomes in patients with low back pain (LBP) (https://pubmed.ncbi.nlm.nih.gov/36914521)
👉It is increasingly recognized that, just like the cells of synovial membrane, resident disc cells and migrated immunocompetent cells possess the ability to mount a robust inflammatory response 🔥 against DAMPs and pathogen-associated molecular patterns (https://pubmed.ncbi.nlm.nih.gov/16508552/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575634/).
👉 Damage-associated molecular patterns (DAMPs), also known as alarmins, and pathogen-associated molecular patterns are molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response 🔥.
👉 These biochemical features have been associated with patterns of structural damage including a condensed and fibrotic ECM, radial fissures, and indentations-herniations of nucleus pulposus into the vertebral endplate, annulus fibrosus rim lesions, delamination, and ingrowth of nerves and vessels in the disrupted otherwise aneural and avascular annulus fibrosus.
👉 Multiple factors including nonphysiological mechanical stresses, genetic predisposition, age-related changes, disc nutritional imbalance, environmental factors including smoking and vibration, as well as diabetes and infection all come into play to disrupt the already fragile and challenging homeostasis of IVDJ tissues (https://pubmed.ncbi.nlm.nih.gov/23015552/, https://pubmed.ncbi.nlm.nih.gov/26562470/ https://pubmed.ncbi.nlm.nih.gov/16915105/, https://pubmed.ncbi.nlm.nih.gov/24753325/, https://pubmed.ncbi.nlm.nih.gov/24436866/)
👉 Primary biochemical features of the degenerated discs include, but are not limited to ECM breakdown including fragmentation and reduced synthesis of proteoglycans, increased levels of inflammatory cytokines including TNF-α, IL-1B, matrix degrading, proteolytic enzymes of the MMP and ADAMTS families and collagen cross-linking in parallel with a synthesis of aberrant types of collagens (fibrosis), the presence of NGF and BDNF and a decrease of TGF-β, as well as a loss of cell density and water (https://pubmed.ncbi.nlm.nih.gov/16915105/, https://pubmed.ncbi.nlm.nih.gov/25827971/, https://pubmed.ncbi.nlm.nih.gov/10870137/, https://pubmed.ncbi.nlm.nih.gov/16508552/, https://pubmed.ncbi.nlm.nih.gov/9250186/).
👉 This structural damage eventually extends into the nucleus pulposus, and leads to an accelerated cell senescence and cell apoptosis (figure, https://pubmed.ncbi.nlm.nih.gov/24753325/, https://pubmed.ncbi.nlm.nih.gov/24436866/, https://pubmed.ncbi.nlm.nih.gov/10851095/, https://pubmed.ncbi.nlm.nih.gov/16816945/
📷 Figure: https://pubmed.ncbi.nlm.nih.gov/29355455/
DAMP: Damage-associated molecular pattern; ECM: Extracellular matrix; MMPs: Matrix-degrading enzymes metalloproteinases; TLRs: Toll-like receptors., ADAMTs: A Disintegrin and Metalloproteinase with Thrombospondin Motifs
