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M2 macrophage-conditioned medium inhibits intervertebral disc degeneration in a tumor necrosis factor-α-rich environment.
- Source :
-
Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2022 Nov; Vol. 40 (11), pp. 2488-2501. Date of Electronic Publication: 2022 Feb 16. - Publication Year :
- 2022
-
Abstract
- Inflammation is the primary pathological phenomenon associated with disc degeneration; the inflammatory cytokine tumor necrosis factor (TNF-α) plays a crucial role in this pathology. The anti-inflammatory and regenerative effects of M2 macrophages on nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IDD) progression remain unknown. Here, M2 conditioned medium (M2CM) was harvested and purified from human acute monocytic leukaemia cell line (THP-1) cells and mouse peritoneal macrophages, respectively; it was used for culturing human NPCs and a mouse intervertebral disc (IVD) organ culture model. NPCs and IVD organ models were divided into three groups: group 1 treated with 10% fetal bovine serum (control); group 2 treated with 10 ng/ml TNF-α; and group 3 treated with 10 ng/ml TNF-α and M2CM (coculture group). After 2-14 days, cell proliferation, extracellular matrix synthesis, apoptosis, and NPC senescence were assessed. Cell proliferation was reduced in TNF-α-treated NPCs and inhibited in the M2CM co-culture treatment. Moreover, TNF-α treatment enhanced apoptosis, senescence, and expression of inflammatory factor-related genes, including interleukin-6, MMP-13, ADAMTS-4, and ADAMTS-5, whereas M2CM coculture significantly reversed these effects. In addition, co-culture with M2CM promoted aggrecan and collagen II synthesis, but reduced collagen Iα1 levels in TNF-α treatment groups. Using our established three-dimensional murine IVD organ culture model, we show that M2CM suppressed the inhibitory effect of TNF-α-rich environment. Therefore, co-culture with M2CM promotes cell proliferation and extracellular matrix synthesis and inhibits inflammation, apoptosis, and NPC senescence. This study highlights the therapeutic potential of M2CM for IDD.<br /> (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)
- Subjects :
- Aggrecans metabolism
Animals
Child
Collagen metabolism
Culture Media, Conditioned metabolism
Culture Media, Conditioned pharmacology
Cytokines metabolism
Humans
Inflammation metabolism
Interleukin-6 metabolism
Macrophages metabolism
Matrix Metalloproteinase 13 metabolism
Mice
Serum Albumin, Bovine metabolism
Serum Albumin, Bovine pharmacology
Serum Albumin, Bovine therapeutic use
Tumor Necrosis Factor-alpha metabolism
Intervertebral Disc pathology
Intervertebral Disc Degeneration pathology
Nucleus Pulposus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-527X
- Volume :
- 40
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of orthopaedic research : official publication of the Orthopaedic Research Society
- Publication Type :
- Academic Journal
- Accession number :
- 35170802
- Full Text :
- https://doi.org/10.1002/jor.25292