Cellular Change in

Chronic Tendinopathies

Meg Greene & Laura Mister, ATS

Melissa Davis, LAT, ATC, Beth Funkhouser, LAT ATC,
Scott Pennington, ATC, SPT, Joseph Vess, Advisor,
Brandon Surber, ATS, & Chandler Copeland, ATS

4/30/2018
 Table of Contents
CLINICAL SCENARIO 1
Development of Clinical Question: 2
Development of Investigation Committee: 2
Focused Clinical Question: 2
Keywords: 2

SUMMARY OF SEARCH METHODOLOGY Error! Bookmark not defined.

Search Strategy: 3
Sources of Evidence Searched: 3
Best Evidence Reviewed: Error! Bookmark not defined.

CLINICAL BOTTOM LINE Error! Bookmark not defined.

Implications for Clinical Practice Error! Bookmark not defined.
Recommendations for Future Research Error! Bookmark not defined.

REFERENCES: 6

CLINICAL SCENARIO
Following our research from last semester where we asked the question, “Is the change in
collagen in chronic tendinitis in physically active people due to an overuse or underuse

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injury,” we concluded that it is still a toss-up as to if tendinopathies are underuse or
overuse. Therefore, we ask our new question in which we seek to find the chemical and
biological causes of tendinopathies in order to clarify questions we still have in
determining if tendinitis is an underuse or overuse injury.

Development of Clinical Question:

This clinical question is a progression of research our team began last semester. Last
semester we sought out to find more information about tendinitis being an underuse
injury. The conclusion of that research left us with little answers and more questions. This
year we decided to further our research of tendinopathies and find if cellular changes could
contribute to or result in chronic tendinopathies. Essentially, we seek to understand how
tendinopathies occur from a chemical and biological standpoint.

Development of Investigation Committee:

Our investigation committee was formed based off of expertise and knowledge on the topic
of chronic tendinopathies. We chose Melissa Davis as our AT advisor because Melissa has a
lot of experience with many different teams. Working with a variety of teams is beneficial
because she has examined and managed tendinopathies in many different regions of the
body. Next we have Beth as our faculty advisor and Scott Pennington as our content expert.
We chose Beth and Scott to be apart of our team because we know they are more involved
in the litterature and would be beneficial to helping us gather essential articles. Next we
have Brandon Surber and Chandler Copland as additional team members to aid in our
research. We chose to have them apart of our team because they have previously
researched tendinopathies for another project. Their knowledge is beneficial to us because
they are able to ask questions about our work that we may not ask ourselves. Finally, we
have Joe Vess as our ampersand center representative. We chose Joe to be on our team
because he is helpful in taking our project to the next level. Joe is the reason we will be able
to present our research this semester. We are excited to show what we have come up with
over this whole school year.

Focused Clinical Question:

In an active population ages 17- 25, could cellular changes in the tendon contribute to or
result in chronic tendinopathies?

Keywords:
Collagen
Cellular change
Inflammation

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Tenocyte

SUMMARY OF SEARCH METHODOLOGY

To answer our clinical question we decided that academic articles would help support our
answer. The articles we decided to review contained the keywords above.

Search Strategy:
Patient: Active population age 17-25
Intervention: Cellular changes
Outcome: Chronic tendinopathies

Sources of Evidence Searched:

EBSCOhost
PubMed
Sources provided by research team

Best Evidence Reviewed:

“Gene expression and matrix turnover in overused and damaged

tendons”

The author Graham Riley discusses the many different types of collagen molecules that can
be identified throughout the body. To start, Riley states there are 27 different collagen
molecules, however, there is little known about the function and tissue distribution of the
more minor collagen fibers, XXI to XXVII. “A normal tendon contains mostly type I collagen,
estimated to represent almost 95% of the total collagen, with smaller amounts of collagen
types III, V, VI, XII and XIV, at levels which are difficult to quantitate by current
methodologies. (Riley, 2004)” Specific fibers types II, IX, X, and XI are found in
fibrocartilage sites, the bond insertion and tendon where it could be compressed. He
identified that different fiber types are associated with different tendons, a tendon holding
more weight will require stronger collagen types. the supraspinatus has significant
reduction in the total collagen content relative to the tissue dry weight, also an increase in
the non-collagen glycoprotein content, as well as increases in matrix proteoglycan. Riley
hypothesized, “An increased matrix turnover is associated with the sub-clinical matrix
degeneration that precedes the clinical condition” (243). Riley found in 1994 type III
collagen was associated with type I collagen fibril bundles by immunohistochemistry. Eight
years later Riley found that a normal supraspinatus tendon had much higher matrix
turnover levels in comparison to a normal biceps brachii tendon. In conclusion tenocytes

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are actively synthesizing and degrading the tendon matrix, the matrix turnover is
important in the tissues response to exercise, strain, and injury (241). As well as some
associated enzymes are required for normal tendon repair, and others may be damaging to
the tendon and responsible for matrix degeneration (248).

“Tendons: Time To Revisit Inflammation?”

Authors Jonathan Ress, Matthew Stride, and Alex Scott discuss many different opinions and
factors of tendinopathies. Their intro begins with a discussion of a paradigm shift between
the understanding of tendinitis as an ‘itis’. They state, “chronic tendinopathy is as entirely
non-inflammatory is an oversimplification to the point of being misleading.” they further
support this statement with the ways clinicians treat tendinitis and make a point that none
of the treatments would decrease the inflammation of the tendon. They continue with their
intro describing another paradigm which states there are two scenarios as to why tendons
fail. First is that it has a poor vascular supply in the first place, and the second is that the
tendon has a failed healing response which it never fully repair itself . This paradigm is
supportive of autologous blood products such as platelet-rich plasma because they believe
the platelets carry nutrients and hormones such as insulin-like growth factor to promote
the healing of the tendon.

The authors then continue on to make a case for inflammation of the tendon. One study
showed that in early stages of a tendinopathy it is void of any inflammatory response cells,
however, 3 week past the initial overload of the tendon they were able to find increased
levels of macrophages, neutrophils, and substance P. Histological studies have shown that
tenocytes may increase in size during an overload. This increases metabolism of the call
and causes the cells to proliferate. “Thus tenocyte hyperplasia and hypertrophy may
provide indirect evidence of up-regulated inflammatory mediators.” Another histological
study talks about regrowth of nerves and vascular vessels. This states that there is evidence
that neoinnervation accompanied by neovessel formation may contribute to or be
responsible for the pain in chronic tendinopathies.

The authors concludes the article with two stances. One, there are some degenerative
pathological processes that are not inflammatory in nature but lead to tendinopathies after
experiencing overuse. Two, more modern research tools have confirmed the presence of
inflammatory cells including macrophages and lymphocytes in chronic tendinopathy. In
addition to inflammatory cells, there is evidence that numerous other chemical mediators
including substance P, MMPs, VEGF and COX which play a role in chronic tendon pathology.

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CLINICAL BOTTOM LINE
In conclusion, there are many factors that play into tendinopathies. To answer the
question, “In an active population ages 17- 25, could cellular changes in the tendon
contribute to or result in chronic tendinopathies,” yes. Tendons have different collagen
types which have different turn over rates. The variation between collagen types could lead
to strengths and weaknesses in the tendon. When the tendon experiences an overuse injury
the weaker collagen could be injured. This leads to the two scenarios as to why a tendon
fails. There are different rates of turnover, so its possible that neoinnervation and
neovascularization may not occur at an appropriate time. The tendon fails due to poor
vascularization, and or it never truly heals itself in the first place due to a failed healing
response. This is evident when we reflect on the study that supported tendonitis as
inflammatory. While the researcher did not see any inflammatory response in the early
stages after overuse to the tendon, three week later they not only found inflammatory cells,
but they found chemical mediators indicative of an inflammatory healing response. This
inflammatory healing response three weeks later is where we believe the collagen matrix
turnover is occuring.

Therefore, we believe the turn over of the collagen matrix, neoinnvervation and
neovascularization, and the inflammatory process all play a role in contributing to
tendinopathies.

Implications for Clinical Practice

Our research implies that the word tendinitis is misleading and inflammation is not the
pure cause of tendinitis. We now see that degeneration of the tendon can be causes by
manythings such as collagen turnover and the body’s failed attempt at healing the tissues.
Inflammation is a secondary result of this break down. The main implication from our
research is that the term tendonitis is too broad of a term and the word tendinopathy
should take its place. Clinicians and patients should be aware that the pain and
inflammation of a tendinopathy is secondary to degeneration of the tendon.

This takes us back to our question from last semester of whether tendinopathies are
overuse or underuse. Our new research implies overuse is the cause of tendon breakdown.
The concept of overuse and underuse is relative. The research stays with the side of
overuse because ultimately activity is what breaks down the tendon, while a lack of
activity would not. This being said there is still a case for underuse because after a long
period of rest, the tendon matrix may change resulting in the tendon being weaker.
Therefore,an overuse activity after a period of underuse would ultimately lead to the
tendinopathy.

Recommendations for Future Research

In the 1990’s pain directly related to the tendon was considered tendinitis, suggesting that
inflammation of the tendon was responsible. That research was accepted and rooted in the
medical literature that we are still reading and referring to, to this day. Treatment has

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stayed relatively the same for over the last twenty years. As early as the 1970’s scientists
have been identifying that it is not due to the chronic inflammation of the tendon however
is the acute inflammation of the cells. However, medical literature has not recognized nor
publicized this information until recently.

In the future, treatment strategies need to evolve along with the research of the true
mechanisms of the injury for the various types of tendinopathies. Also the term
“tendonitis” needs to be properly defined and moved away from as such a broad term.
Therefore, if research could open the door to a identifying the different tendinopathies and
cause of pain, major changes in treatment, recovery, and management could take place.

REFERENCES:
Riley, G. P. (2005). Gene expression and matrix turnover in overused and damaged
tendons. Scandinavian Journal of Medicine and Science in Sports,15(4), 241-251.
doi:10.1111/j.1600-0838.2005.00456.x

Rees, J. D., Stride, M., & Scott, A. (2013). Tendons: Time To Revisit Inflammation? British
Journal of Sports Medicine,47(9). doi:10.1136/bjsports-2013-092459.9