Is Apoptosis the Cause of Noninsertional Achilles Tendinopathy

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Is Apoptosis the Cause of Noninsertional Achilles Tendinopathy
Christopher J. Pearce, Muhammad Ismail, James D. Calder,
American Journal of Sports Medicine (in press)

 

Apoptosis

Programmed cell death in multicellular organisms

Apoptosis (from Ancient Greek: ἀπόπτωσις, romanized: apóptōsis, lit. 'falling off') is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast.^[1] Biochemical events lead to characteristic cell changes (morphology) and death.^[2] These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis.^[a] For an average human child between eight and fourteen years old, each day the approximate loss is 20 to 30 billion cells.^[4]

In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytes are able to engulf and remove before the contents of the cell can spill out onto surrounding cells and cause damage to them.^[5]

Because apoptosis cannot stop once it has begun, it is a highly regulated process. Apoptosis can be initiated through one of two pathways. In the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. Weak external signals may also activate the intrinsic pathway of apoptosis.^[6] Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately.

In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer. Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis.^[7]

1. ^ Green D (2011). Means to an End: Apoptosis and other Cell Death Mechanisms. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN 978-0-87969-888-1. Archived from the original on 2020-07-26. Retrieved 2020-05-25.
2. ^ Böhm I, Schild H (2003). "Apoptosis: the complex scenario for a silent cell death". Mol Imaging Biol. 5 (1): 2–14. doi:10.1016/S1536-1632(03)00024-6. PMID 14499155.
3. ^ Alberts, p. 2.
4. ^ Karam JA (2009). Apoptosis in Carcinogenesis and Chemotherapy. Netherlands: Springer. ISBN 978-1-4020-9597-9.
5. ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008). "Chapter 18 Apoptosis: Programmed Cell Death Eliminates Unwanted Cells". Molecular Biology of the Cell (textbook) (5th ed.). Garland Science. p. 1115. ISBN 978-0-8153-4105-5.
6. ^ Raychaudhuri S (August 2010). "A minimal model of signaling network elucidates cell-to-cell stochastic variability in apoptosis". PLOS ONE. 5 (8): e11930. arXiv:1009.2294. Bibcode:2010PLoSO...511930R. doi:10.1371/journal.pone.0011930. PMC 2920308. PMID 20711445.
7. ^ Elmore S (June 2007). "Apoptosis: A Review of Programmed Cell Death". Toxicologic Pathology. 35 (4): 495–516. doi:10.1080/01926230701320337. PMC 2117903. PMID 17562483.

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ok, but why do the tissues or the cell begin to die or shut down?

What functional or structural mechanism precedes or leads to Apoptosis in tissues, especiall the Achilles non-insertional or otherwise?

What takes us from inflammatory stage to non-inflammatory Apoptosis in these tissues?

I think we will find that this will be true tissue stress as Eric has described many times in the past.

I think dysfunction of the AJ will lead to overuse of the gastro-soleus complex due to lack of return loading in the AJ. If you don't DF the AJ enough adn timely enough you will not get energy return adn teh muscle tendon complex will overtax itself adn then begin to breakdown. Inflammation first, then apparently Apoptosis.

The next step is to see if the Apoptosis can be reversed thru a return of proper function in the AJ. That I think would prove my hypothesis at least. Time will tell.

Cheers!
Bruce

 

Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case–control cohort
Rebecca Rickby, Louis El Khoury, William J. Ribbans, Stuart M. Raleigh,
Gene; Available online 5 June 2015