Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology

Hansen, Philip; Haraldsson, Bjarki Thor; Aagaard, Per; Kovanen, Vuokko; Avery, Nicholas C.; Qvortrup, Klaus; Larsen, Jacob Norvig; Krogsgaard, Michael; Kjær, Michael; Magnusson, S. Peter

doi:10.1152/japplphysiol.00944.2009

Cited by 76 publications

(69 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This echoes previous studies investigating the effects of AGEs in tendon Danielsen and Andreassen, 1988;Reddy et al, 2002;Reddy, 2004;Fessel et al, 2012). However, these findings contradict reports of altered elastic properties in studies on the mechanical properties of aged animal tendons (Vogel, 1978;Dressler et al, 2002;Goh et al, 2008) and on human patellar tendons explants (Blevins et al, 1994;Flahiff et al, 1995;Lewis and Shaw, 1997;Hansen et al, 2010). Such conflicting results clearly suggest that either numerous competing factors can affect tendon stiffness/modulus in the aging process: changes in cross sectional area, age-related differences in water and type-1 collagen content (Couppé et al, 2009), and/or an increase in type V collagen (Magnusson et al, 2008), among others.…”

Section: Discussionsupporting

confidence: 78%

“…These changes correlate to clinically relevant loss of tissue function (Abate et al, 2011;Fox et al, 2011), increased susceptibility to damage and injury (Dressler et al, 2002), and reduced potential for healing (Bedi et al, 2010). While age-related changes in tendon tissue have been associated with increased stiffness and higher failure, a concurrent age-associated loss of tendon mechanical integrity has been reported for both animals (Vogel, 1978;Dressler et al, 2002;Goh et al, 2008) and humans (Blevins et al, 1994;Flahiff et al, 1995;Lewis and Shaw, 1997;Hansen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Advanced glycation end-products diminish tendon collagen fiber sliding

et al. 2013

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Advanced glycation end-products diminish tendon collagen fiber sliding

et al. 2013

View full text Add to dashboard Cite

“…LOX-derived cross-linking increases during adult tendon aging and wound healing (14,40), and it is believed to contribute significantly to mature tendon mechanical properties, although reports are inconsistent. LOX-derived hydroxylysyl pyridinoline (HP) cross-linking density was significantly correlated to elastic modulus in goat patellar tendon (41) but not in equine superficial digital flexor tendon (42) or human patellar tendon (43). In contrast, there are limited data of collagen cross-linking in embryonic tendon, and the focus was on a single embryonic time point without examining mechanical contributions (44).…”

Section: Discussionmentioning

confidence: 99%

Characterization of mechanical and biochemical properties of developing embryonic tendon

Marturano

Arena

Schiller

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

167

277

View full text Add to dashboard Cite

Tendons have uniquely high tensile strength, critical to their function to transfer force from muscle to bone. When injured, their innate healing response results in aberrant matrix organization and functional properties. Efforts to regenerate tendon are challenged by limited understanding of its normal development. Consequently, there are few known markers to assess tendon formation and parameters to design tissue engineering scaffolds. We profiled mechanical and biological properties of embryonic tendon and demonstrated functional properties of developing tendon are not wholly reflected by protein expression and tissue morphology. Using force volume-atomic force microscopy, we found that nano-and microscale tendon elastic moduli increase nonlinearly and become increasingly spatially heterogeneous during embryonic development. When we analyzed potential biochemical contributors to modulus, we found statistically significant but weak correlation between elastic modulus and collagen content, and no correlation with DNA or glycosaminoglycan content, indicating there are additional contributors to mechanical properties. To investigate collagen cross-linking as a potential contributor, we inhibited lysyl oxidasemediated collagen cross-linking, which significantly reduced tendon elastic modulus without affecting collagen morphology or DNA, glycosaminoglycan, and collagen content. This suggests that lysyl oxidase-mediated cross-linking plays a significant role in the development of embryonic tendon functional properties and demonstrates that changes in cross-links alter mechanical properties without affecting matrix content and organization. Taken together, these data demonstrate the importance of functional markers to assess tendon development and provide a profile of tenogenic mechanical properties that may be implemented in tissue engineering scaffold design to mechanoregulate new tendon regeneration.musculoskeletal | second harmonic generation T endon is a principal tissue involved in movement, functioning primarily to transfer loads from muscle to bone. Acute and chronic tendon injuries are significant clinical problems due to poor innate healing ability and drawbacks associated with surgical repair (1, 2). In 2006, musculoskeletal symptoms were the second most frequent reason for physician visits in the United States, resulting in over 130 million visits at a cost of nearly $850 billion (3). Almost half of these visits involved tendons and ligaments, with incidence expected to rise with an aging population. Thus, efforts have focused on engineering new tissues for replacement, although this has been challenged by a paucity of markers with which to assess functional tendon development and few known cues to direct differentiation and new tissue formation.Characterization of tendon formation in embryonic or engineered tissue has typically relied on molecular markers, as well as matrix composition and organization (4-9). Although useful for assessing cell differentiation and ECM deposition during tissue formation, t...

show abstract

“…Tendon mechanics were measured as described previously (19). In summary, a micro-tensile testing stage was used for the mechanical testing of the Achilles tendon bundle dissected from the rats.…”

Section: Mechanical Testingmentioning

confidence: 99%

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

Heinemeier

Skovgaard

Bayer

et al. 2012

Journal of Applied Physiology

View full text Add to dashboard Cite

Little is known about the etiology of this disorder, and the development of a good animal model for overuse tendinopathy is essential for advancing insight into the disease mechanisms. Our aim was to test a previously proposed rat model for Achilles tendon overuse. Ten adult male Sprague-Dawley rats ran on a treadmill with 10°incline, 1 h/day, 5 days/wk (17-20 m/min) for 12 wk and were compared with 12 control rats. Histological, mechanical, and gene-expression changes were measured on the Achilles tendons after the intervention, and local tendon glucose-uptake was measured before and after the intervention with positron emission tomography. No differences were detected between runners and controls in tissue histology or in glucose uptake, indicating that tendon pathology was not induced. Greater tendon tissue modulus (P Ͻ 0.005) and failure stress/body weight (P Ͻ 0.02) in runners compared with controls further supported that tendons successfully adapted to uphill running. Several genes of interest were regulated after 12 wk of running. Expression of collagen III and insulin-like growth factor I was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-␤1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading. loading; exercise; tendinopathy; collagen TENDONS TRANSMIT FORCE FROM muscle to bone during muscle contraction, and optimal, painless function of tendon tissue is essential in voluntary movement. Although tendons can withstand considerable force, repetitive movements can lead to overuse of tendon tissue, resulting in tendinopathy, which is characterized by pain during activity and significantly impaired performance (36). Tendinopathy is very common in relation to both sports and occupational loading (16,17,45), and, since treatment possibilities are still relatively poor, these conditions are often prolonged (36). Although the features of tendinopathy at the time point when symptoms occur are relatively well described, the etiology of overuse-related tendinopathy is still poorly understood. Thus we know that symptomatic human tendinopathy is characterized by histological changes, such as increased cell density, altered cell morphology, and disorganization of the collagen matrix (reviewed by Ref. 36). In addition, increased vascularization has been shown in tendinopathic tendon (8), and studies of gene expression commonly find higher levels of collagen I and III, proteoglycan, and matrix metalloproteinase (MMP)-2 mRNA, as well as decreased MMP-3 mRNA expression (3, 12-14, 26 -28). However, the events leading up to these chan...

show abstract

Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology

Cited by 76 publications

References 38 publications

Advanced glycation end-products diminish tendon collagen fiber sliding

Advanced glycation end-products diminish tendon collagen fiber sliding

Characterization of mechanical and biochemical properties of developing embryonic tendon

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

Contact Info

Product

Resources

About