Mechanical loading inhibits cartilage inflammatory signalling via an HDAC6 and IFT-dependent mechanism regulating primary cilia elongation
PainSci summary of Fu 2019?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible. ★★★★☆?4-star ratings are for bigger/better studies and reviews published in more prestigious journals, with only quibbles. Ratings are a highly subjective opinion, and subject to revision at any time. If you think this paper has been incorrectly rated, please let me know.
This is a highly technical petri-dish study of the effect of “exercise” (mechanical loading) on the inflammation of cartilage cells. Basically, they mechanically stressed samples of excised cartilage and cartilage cells. The surprising, good-news result was that the researchers reported that loading actually reduced inflammation (inflammatory signals produced by the cells).
While it is a near certainly that too much loading would increase inflammatory signalling, it is nifty that mechanical loading in the Goldilocks zone might actually be anti-inflammatory. It implies a very specific and substantive way in which “exercise is medicine.”
original abstract†Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
OBJECTIVE: Physiological mechanical loading reduces inflammatory signalling in numerous cell types including articular chondrocytes however the mechanism responsible remains unclear. This study investigates the role of chondrocyte primary cilia and associated intraflagellar transport (IFT) in the mechanical regulation of interleukin-1β (IL-1β) signalling. DESIGN: Isolated chondrocytes and cartilage explants were subjected to cyclic mechanical loading in the presence and absence of the cytokine IL-1β. Nitric oxide (NO) and prostaglandin E2 (PGE2) release were used to monitor IL-1β signalling whilst Sulphated glycosaminoglycan (sGAG) release provided measurement of cartilage degradation. Measurements were made of HDAC6 activity and tubulin polymerisation and acetylation. Effects on primary cilia were monitored by confocal and super resolution microscopy. Involvement of IFT was analysed using ORPK cells with hypomorphic mutation of IFT88. RESULTS: Mechanical loading suppressed NO and PGE2 release and prevented cartilage degradation. Loading activated HDAC6 and disrupted tubulin acetylation and cilia elongation induced by IL-1β. HDAC6 inhibition with tubacin blocked the anti-inflammatory effects of loading and restored tubulin acetylation and cilia elongation. Hypomorphic mutation of IFT88 reduced IL-1β signalling and abolished the anti-inflammatory effects of loading indicating the mechanism is IFT-dependent. Loading reduced the pool of non-polymerised tubulin which was replicated by taxol which also mimicked the anti-inflammatory effects of mechanical loading and prevented cilia elongation. CONCLUSIONS: This study reveals that mechanical loading suppresses inflammatory signalling, partially dependent on IFT, by activation of HDAC6 and post transcriptional modulation of tubulin.
related content
These three articles on PainScience.com cite Fu 2019 as a source:
- PS PF-ROM Exercises — ‘Pain-free range of motion’ or early mobilization exercises can help you heal
- PS Voltaren® Gel Review — A useful rub-on anti-inflammatory medication for arthritis, tendonitis, bursitis, runner’s knee, and muscle strain
- PS Repetitive Strain Injuries Tutorial — Five surprising and important facts about repetitive strain injuries like carpal tunnel syndrome, tendinitis, or iliotibial band syndrome
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- A Bayesian model-averaged meta-analysis of the power pose effect with informed and default priors: the case of felt power. Gronau 2017 Comprehensive Results in Social Psychology.
- The neck and headaches. Bogduk 2014 Neurol Clin.
- Agreement of self-reported items and clinically assessed nerve root involvement (or sciatica) in a primary care setting. Konstantinou 2012 Eur Spine J.
- Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. Morelli 2017 Am J Sports Med.
- Association of Spinal Manipulative Therapy With Clinical Benefit and Harm for Acute Low Back Pain: Systematic Review and Meta-analysis. Paige 2017 JAMA.