Cells

Reducing a protein lowered inflammatory signals in human disc cells

Experiments using cells from four donors found lower activity of inflammatory genes and higher activity of genes associated with the supporting material around cells.

Figure 1. Study Design. (a) Lumbar IVDs from 20-month-old female and male WT and KO mice were collected for histological and immunohistochemical analyses.
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Figure 1. Study Design. (a) Lumbar IVDs from 20-month-old female and male WT and KO mice were collected for histological and immunohistochemical analyses.Study Design. (a) Lumbar IVDs from 20-month-old female and male WT and KO mice were collected for histological and immunohistochemical analyses.Chatterjee et al.

Our read

Mechanisms
Studied:
Experiments in human cells
What changed:
Human disc cells with reduced PHLPP1 had lower activity of genes for inflammatory signals than controls given non-targeting RNA
The catch:
Gene-activity analysis used cells from only four donors
In the record:
One of 6 papers on PHLPP1 on record: 3 with results in people, 1 in animals.
Why it’s aging research:
Old against young, or naturally aged tissue.

Editor of record: Boris Djordjevic · AgingResearch.News

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Researchers experimented with human nucleus pulposus cells, which come from the soft center of spinal discs, taken from degenerated discs removed during surgery for back pain. They used targeted RNA molecules to reduce PHLPP1, a protein that regulates cell signaling, and compared the cells with controls given non-targeting RNA. Gene-activity analysis used cells from four donors.

Reducing PHLPP1 lowered activity of genes for inflammatory signals and enzymes that break down the material surrounding cells. It increased activity of genes associated with that material. It also dampened responses to an inflammation-triggering protein. In a separate animal experiment, 20-month-old mice lacking the gene had less disc degeneration and lower levels of inflammatory signals. The protective effects were most apparent in males.

Why it matters

Age-related spinal disc degeneration contributes to low back pain. The authors proposed inhibiting PHLPP1 as a potential way to alter the course of disc degeneration.

Caveats

The human experiments tested cells grown in the lab, not pain relief or disc recovery in people. The mouse analysis excluded animals that died or required euthanasia before 20 months.

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