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Home / Equine Research Bank / J Biol Chem / Aspartic acid racemization and collagen degradation markers ...
The Journal of biological chemistry2010; 285(21); 15674-15681; doi: 10.1074/jbc.M109.077503

Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging.

Abstract: Little is known about the rate at which protein turnover occurs in living tendon and whether the rate differs between tendons with different physiological roles. In this study, we have quantified the racemization of aspartic acid to calculate the age of the collagenous and non-collagenous components of the high strain injury-prone superficial digital flexor tendon (SDFT) and low strain rarely injured common digital extensor tendon (CDET) in a group of horses with a wide age range. In addition, the turnover of collagen was assessed indirectly by measuring the levels of collagen degradation markers (collagenase-generated neoepitope and cross-linked telopeptide of type I collagen). The fractional increase in D-Asp was similar (p = 0.7) in the SDFT (5.87 x 10(-4)/year) and CDET (5.82 x 10(-4)/year) tissue, and D/L-Asp ratios showed a good correlation with pentosidine levels. We calculated a mean (+/-S.E.) collagen half-life of 197.53 (+/-18.23) years for the SDFT, which increased significantly with horse age (p = 0.03) and was significantly (p < 0.001) higher than that for the CDET (34.03 (+/-3.39) years). Using similar calculations, the half-life of non-collagenous protein was 2.18 (+/-0.41) years in the SDFT and was significantly (p = 0.04) lower than the value of 3.51 (+/-0.51) years for the CDET. Collagen degradation markers were higher in the CDET and suggested an accumulation of partially degraded collagen within the matrix with aging in the SDFT. We propose that increased susceptibility to injury in older individuals results from an inability to remove partially degraded collagen from the matrix leading to reduced mechanical competence.
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Publication Date: 2010-03-22 PubMed ID: 20308077PubMed Central: PMC2871433DOI: 10.1074/jbc.M109.077503Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines the rate of protein turnover in tendon tissues, using aspartic acid and collagen degradation markers to investigate damage accumulation in tendons as associated with aging.

Protein Turnover in Tendons

  • The study examines the protein turnover in tendons, specifically looking at a pair of tendons in horses – the superficial digital flexor tendon (SDFT) known to be prone to high strain injury, and the common digital extensor tendon (CDET) that is less susceptible.
  • The investigators applied aspartic acid racemization, a natural process that occurs in proteins over time, to estimate the age of the collagenous and non-collagenous components in these tendons.
  • Turnover of collagen was evaluated indirectly by measuring the levels of collagen degradation markers, providing insight into collagen damage.

The Findings about Tendon Collagen Aging

  • The racemization rate was similar in both the SDFT and CDET tissue, suggesting that the overall process of aging may not significantly differ between tendons with different strain characteristics.
  • D/L-Asp ratios, indicating the amount of D and L isomers of aspartic acid, showed good correlation with pentosidine levels, which are biomarkers of aging and metabolic stress.
  • The half-life of collagen in the injury-prone SDFT was substantially longer at around 197.5 years, compared to 34 years in the more resilient CDET. Interestingly, the collagen half-life in the SDFT was found to increase significantly with the horse’s age.

Degradation Rate Differences between Tendons

  • In terms of non-collagenous protein, SDFT has a shorter half-life (2.18 years) compared to CDET (3.51 years), indicating a faster turnover of these proteins in the high strain tendon.
  • Collagen degradation markers were found to be higher in the often uninjured CDET than the SDFT, suggesting a higher rate of collagen turnover in the less injury-prone tendon.
  • This suggests that as tendons age, there’s an accumulation of partially degraded collagen in the matrix, particularly in the case of injury-prone SDFT.
  • This accumulation could be the result of a decreased ability to remove degraded collagen, which could lead to reduced mechanical competence, thereby increasing susceptibility to injury in aged or high-strain tendons.

Cite This Article

APA
Thorpe CT, Streeter I, Pinchbeck GL, Goodship AE, Clegg PD, Birch HL. (2010). Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging. J Biol Chem, 285(21), 15674-15681. https://doi.org/10.1074/jbc.M109.077503

Publication

The Journal of biological chemistry
ISSN: 1083-351X
NlmUniqueID: 2985121R
Country: United States
Language: English
Volume: 285
Issue: 21
Pages: 15674-15681

Researcher Affiliations

Thorpe, Chavaunne T
  • Division of Surgery and Interventional Science, University College London, Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, London, UK. rejacth@ucl.ac.uk
Streeter, Ian
    Pinchbeck, Gina L
      Goodship, Allen E
        Clegg, Peter D
          Birch, Helen L

            MeSH Terms

            • Aging / metabolism
            • Aging / pathology
            • Animals
            • Aspartic Acid / metabolism
            • Biomarkers / metabolism
            • Collagen Type I / metabolism
            • Female
            • Horses
            • Male
            • Tendon Injuries / metabolism
            • Tendon Injuries / pathology
            • Tendons / metabolism
            • Tendons / pathology

            Grant Funding

            • G0700869 / Medical Research Council

            References

            This article includes 42 references
            1. Ker RF. The implications of the adaptable fatigue quality of tendons for their construction, repair and function.. Comp Biochem Physiol A Mol Integr Physiol 2002 Dec;133(4):987-1000.
              pubmed: 12485688doi: 10.1016/s1095-6433(02)00171-xgoogle scholar: lookup
            2. Biewener AA. Muscle-tendon stresses and elastic energy storage during locomotion in the horse.. Comp Biochem Physiol B Biochem Mol Biol 1998 May;120(1):73-87.
              pubmed: 9787779doi: 10.1016/s0305-0491(98)00024-8google scholar: lookup
            3. Birch HL, Worboys S, Eissa S, Jackson B, Strassburg S, Clegg PD. Matrix metabolism rate differs in functionally distinct tendons.. Matrix Biol 2008 Apr;27(3):182-9.
              pubmed: 18032005doi: 10.1016/j.matbio.2007.10.004google scholar: lookup
            4. Scott JE. Elasticity in extracellular matrix 'shape modules' of tendon, cartilage, etc. A sliding proteoglycan-filament model.. J Physiol 2003 Dec 1;553(Pt 2):335-43.
              pmc: PMC2343561pubmed: 12923209doi: 10.1113/jphysiol.2003.050179google scholar: lookup
            5. Miller BF, Olesen JL, Hansen M, Døssing S, Crameri RM, Welling RJ, Langberg H, Flyvbjerg A, Kjaer M, Babraj JA, Smith K, Rennie MJ. Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise.. J Physiol 2005 Sep 15;567(Pt 3):1021-33.
              pmc: PMC1474228pubmed: 16002437doi: 10.1113/jphysiol.2005.093690google scholar: lookup
            6. Rees JD, Wilson AM, Wolman RL. Current concepts in the management of tendon disorders.. Rheumatology (Oxford) 2006 May;45(5):508-21.
              pubmed: 16490749doi: 10.1093/rheumatology/kel046google scholar: lookup
            7. Birch HL, Bailey JV, Bailey AJ, Goodship AE. Age-related changes to the molecular and cellular components of equine flexor tendons.. Equine Vet J 1999 Sep;31(5):391-6.
              pubmed: 10505954doi: 10.1111/j.2042-3306.1999.tb03838.xgoogle scholar: lookup
            8. Lin YL, Brama PA, Kiers GH, van Weeren PR, DeGroot J. Extracellular matrix composition of the equine superficial digital flexor tendon: relationship with age and anatomical site.. J Vet Med A Physiol Pathol Clin Med 2005 Sep;52(7):333-8.
              pubmed: 16109099doi: 10.1111/j.1439-0442.2005.00742.xgoogle scholar: lookup
            9. Birch H. L., Smith T. J., Draper E. R., Bailey A. J., Avery N. C., Goodship A. E. (2006) Matrix Biol. 25, 74
            10. Bada JL. In vivo racemization in mammalian proteins.. Methods Enzymol 1984;106:98-115.
              pubmed: 6493067doi: 10.1016/0076-6879(84)06011-0google scholar: lookup
            11. Maroudas A, Bayliss MT, Uchitel-Kaushansky N, Schneiderman R, Gilav E. Aggrecan turnover in human articular cartilage: use of aspartic acid racemization as a marker of molecular age.. Arch Biochem Biophys 1998 Feb 1;350(1):61-71.
              pubmed: 9466821doi: 10.1006/abbi.1997.0492google scholar: lookup
            12. Sivan SS, Tsitron E, Wachtel E, Roughley PJ, Sakkee N, van der Ham F, DeGroot J, Roberts S, Maroudas A. Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid.. J Biol Chem 2006 May 12;281(19):13009-13014.
              pubmed: 16537531doi: 10.1074/jbc.m600296200google scholar: lookup
            13. Sivan SS, Tsitron E, Wachtel E, Roughley P, Sakkee N, van der Ham F, Degroot J, Maroudas A. Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs.. Biochem J 2006 Oct 1;399(1):29-35.
              pmc: PMC1570172pubmed: 16787390doi: 10.1042/bj20060579google scholar: lookup
            14. Sivan SS, Wachtel E, Tsitron E, Sakkee N, van der Ham F, Degroot J, Roberts S, Maroudas A. Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid.. J Biol Chem 2008 Apr 4;283(14):8796-801.
              pubmed: 18250164doi: 10.1074/jbc.m709885200google scholar: lookup
            15. Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ, Bijlsma JW, Lafeber FP, Baynes JW, TeKoppele JM. Effect of collagen turnover on the accumulation of advanced glycation end products.. J Biol Chem 2000 Dec 15;275(50):39027-31.
              pubmed: 10976109doi: 10.1074/jbc.m006700200google scholar: lookup
            16. Langberg H, Skovgaard D, Petersen LJ, Bulow J, Kjaer M. Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans.. J Physiol 1999 Nov 15;521 Pt 1(Pt 1):299-306.
              pmc: PMC2269635pubmed: 10562353doi: 10.1111/j.1469-7793.1999.00299.xgoogle scholar: lookup
            17. Frisbie DD, Al-Sobayil F, Billinghurst RC, Kawcak CE, McIlwraith CW. Changes in synovial fluid and serum biomarkers with exercise and early osteoarthritis in horses.. Osteoarthritis Cartilage 2008 Oct;16(10):1196-204.
              pubmed: 18442931doi: 10.1016/j.joca.2008.03.008google scholar: lookup
            18. Birch HL, Bailey AJ, Goodship AE. Macroscopic 'degeneration' of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition.. Equine Vet J 1998 Nov;30(6):534-9.
              pubmed: 9844973doi: 10.1111/j.2042-3306.1998.tb04530.xgoogle scholar: lookup
            19. Yekkala R, Meers C, Hoogmartens J, Lambrichts I, Willems G, Van Schepdael A. An improved sample preparation for an LC method used in the age estimation based on aspartic acid racemization from human dentin.. J Sep Sci 2007 Jan;30(1):118-21.
              pubmed: 17313150doi: 10.1002/jssc.200600191google scholar: lookup
            20. Helfman PM, Bada JL. Aspartic acid racemisation in dentine as a measure of ageing.. Nature 1976 Jul 22;262(5566):279-81.
              pubmed: 958370doi: 10.1038/262279b0google scholar: lookup
            21. Fanibunda KB. Diagnosis of tooth vitality by crown surface temperature measurement: a clinical evaluation.. J Dent 1986 Aug;14(4):160-4.
              pubmed: 3463588doi: 10.1016/0300-5712(86)90018-7google scholar: lookup
            22. Wilson AM, Goodship AE. Exercise-induced hyperthermia as a possible mechanism for tendon degeneration.. J Biomech 1994 Jul;27(7):899-905.
              pubmed: 8063840doi: 10.1016/0021-9290(94)90262-3google scholar: lookup
            23. Bada J. L., Kvenvolden K. A., Peterson E. T. (1973) Nature 245, 308–310
            24. Maroudas A, Palla G, Gilav E. Racemization of aspartic acid in human articular cartilage.. Connect Tissue Res 1992;28(3):161-9.
              pubmed: 1468204doi: 10.3109/03008209209015033google scholar: lookup
            25. Becher C, Springer J, Feil S, Cerulli G, Paessler HH. Intra-articular temperatures of the knee in sports - an in-vivo study of jogging and alpine skiing.. BMC Musculoskelet Disord 2008 Apr 11;9:46.
              pmc: PMC2330048pubmed: 18405365doi: 10.1186/1471-2474-9-46google scholar: lookup
            26. Bailey AJ, Sims TJ, Avery NC, Halligan EP. Non-enzymic glycation of fibrous collagen: reaction products of glucose and ribose.. Biochem J 1995 Jan 15;305 ( Pt 2)(Pt 2):385-90.
              pmc: PMC1136373pubmed: 7832750doi: 10.1042/bj3050385google scholar: lookup
            27. Bergman I., Loxley R. (1963) Analyt. Chem. 35, 1961–1965
            28. Bannister DW, Burns AB. Adaptation of the Bergman and Loxley technique for hydroxyproline determination to the autoanalyzer and its use in determining plasma hydroxyproline in the domestic fowl.. Analyst 1970 Jun;95(131):596-600.
              pubmed: 4911884doi: 10.1039/an9709500596google scholar: lookup
            29. Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue.. Biochim Biophys Acta 1986 Sep 4;883(2):173-7.
              pubmed: 3091074doi: 10.1016/0304-4165(86)90306-5google scholar: lookup
            30. Riley GP, Curry V, DeGroot J, van El B, Verzijl N, Hazleman BL, Bank RA. Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology.. Matrix Biol 2002 Mar;21(2):185-95.
              pubmed: 11852234doi: 10.1016/s0945-053x(01)00196-2google scholar: lookup
            31. Verzijl N, DeGroot J, Bank RA, Bayliss MT, Bijlsma JW, Lafeber FP, Maroudas A, TeKoppele JM. Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: the use of pentosidine levels as a quantitative measure of protein turnover.. Matrix Biol 2001 Nov;20(7):409-17.
              pubmed: 11691581doi: 10.1016/s0945-053x(01)00158-5google scholar: lookup
            32. Laurent GJ. Dynamic state of collagen: pathways of collagen degradation in vivo and their possible role in regulation of collagen mass.. Am J Physiol 1987 Jan;252(1 Pt 1):C1-9.
              pubmed: 3544859doi: 10.1152/ajpcell.1987.252.1.c1google scholar: lookup
            33. Rees SG, Flannery CR, Little CB, Hughes CE, Caterson B, Dent CM. Catabolism of aggrecan, decorin and biglycan in tendon.. Biochem J 2000 Aug 15;350 Pt 1(Pt 1):181-8.
              pmc: PMC1221240pubmed: 10926842
            34. Puxkandl R, Zizak I, Paris O, Keckes J, Tesch W, Bernstorff S, Purslow P, Fratzl P. Viscoelastic properties of collagen: synchrotron radiation investigations and structural model.. Philos Trans R Soc Lond B Biol Sci 2002 Feb 28;357(1418):191-7.
              pmc: PMC1692933pubmed: 11911776doi: 10.1098/rstb.2001.1033google scholar: lookup
            35. Langberg H, Rosendal L, Kjaer M. Training-induced changes in peritendinous type I collagen turnover determined by microdialysis in humans.. J Physiol 2001 Jul 1;534(Pt 1):297-302.
              pmc: PMC2278680pubmed: 11433010doi: 10.1111/j.1469-7793.2001.00297.xgoogle scholar: lookup
            36. Perumal S, Antipova O, Orgel JP. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.. Proc Natl Acad Sci U S A 2008 Feb 26;105(8):2824-9.
              pmc: PMC2268544pubmed: 18287018doi: 10.1073/pnas.0710588105google scholar: lookup
            37. Birch HL. Tendon matrix composition and turnover in relation to functional requirements.. Int J Exp Pathol 2007 Aug;88(4):241-8.
              pmc: PMC2517317pubmed: 17696905doi: 10.1111/j.1365-2613.2007.00552.xgoogle scholar: lookup
            38. Wu JJ, Lark MW, Chun LE, Eyre DR. Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage.. J Biol Chem 1991 Mar 25;266(9):5625-8.
              pubmed: 2005102
            39. van Duin A. C. T., Collins M. J. (1998) Organic Geochem. 29, 1227–1232
            40. Sell DR, Biemel KM, Reihl O, Lederer MO, Strauch CM, Monnier VM. Glucosepane is a major protein cross-link of the senescent human extracellular matrix. Relationship with diabetes.. J Biol Chem 2005 Apr 1;280(13):12310-5.
              pubmed: 15677467doi: 10.1074/jbc.m500733200google scholar: lookup
            41. Reddy GK, Stehno-Bittel L, Enwemeka CS. Glycation-induced matrix stability in the rabbit achilles tendon.. Arch Biochem Biophys 2002 Mar 15;399(2):174-80.
              pubmed: 11888203doi: 10.1006/abbi.2001.2747google scholar: lookup
            42. Monnier VM, Sell DR, Dai Z, Nemet I, Collard F, Zhang J. The role of the amadori product in the complications of diabetes.. Ann N Y Acad Sci 2008 Apr;1126:81-8.
              pubmed: 18448799doi: 10.1196/annals.1433.052google scholar: lookup

            Citations

            This article has been cited 69 times.
            1. Gsell KY, Veres SP, Kreplak L. Single collagen fibrils isolated from high stress and low stress tendons show differing susceptibility to enzymatic degradation by the interstitial collagenase matrix metalloproteinase-1 (MMP-1).. Matrix Biol Plus 2023 Jun;18:100129.
              doi: 10.1016/j.mbplus.2023.100129pubmed: 36915648google scholar: lookup
            2. Bautista CA, Srikumar A, Tichy ED, Qian G, Jiang X, Qin L, Mourkioti F, Dyment NA. CD206+ tendon resident macrophages and their potential crosstalk with fibroblasts and the ECM during tendon growth and maturation.. Front Physiol 2023;14:1122348.
              doi: 10.3389/fphys.2023.1122348pubmed: 36909235google scholar: lookup
            3. Yin NH, Parker AW, Matousek P, Birch HL. Chemical Markers of Human Tendon Health Identified Using Raman Spectroscopy: Potential for In Vivo Assessment.. Int J Mol Sci 2022 Nov 27;23(23).
              doi: 10.3390/ijms232314854pubmed: 36499181google scholar: lookup
            4. Kharaz YA, Goljanek-Whysall K, Nye G, Hurst JL, McArdle A, Comerford EJ. Age-related changes in microRNAs expression in cruciate ligaments of wild-stock house mice.. Physiol Rep 2022 Aug;10(16):e15426.
              doi: 10.14814/phy2.15426pubmed: 35993414google scholar: lookup
            5. Matsubayashi Y. Dynamic movement and turnover of extracellular matrices during tissue development and maintenance.. Fly (Austin) 2022 Dec;16(1):248-274.
              doi: 10.1080/19336934.2022.2076539pubmed: 35856387google scholar: lookup
            6. Ellingson AJ, Pancheri NM, Schiele NR. Regulators of collagen crosslinking in developing and adult tendons.. Eur Cell Mater 2022 Apr 5;43:130-152.
              doi: 10.22203/eCM.v043a11pubmed: 35380167google scholar: lookup
            7. Siadat SM, Zamboulis DE, Thorpe CT, Ruberti JW, Connizzo BK. Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life.. Adv Exp Med Biol 2021;1348:45-103.
              doi: 10.1007/978-3-030-80614-9_3pubmed: 34807415google scholar: lookup
            8. Nash A, Notou M, Lopez-Clavijo AF, Bozec L, de Leeuw NH, Birch HL. Glucosepane is associated with changes to structural and physical properties of collagen fibrils.. Matrix Biol Plus 2019 Nov;4:100013.
              doi: 10.1016/j.mbplus.2019.100013pubmed: 33543010google scholar: lookup
            9. Nash A, Noh SY, Birch HL, de Leeuw NH. Lysine-arginine advanced glycation end-product cross-links and the effect on collagen structure: A molecular dynamics study.. Proteins 2021 May;89(5):521-530.
              doi: 10.1002/prot.26036pubmed: 33320391google scholar: lookup
            10. Li Z, Du T, Ruan C, Niu X. Bioinspired mineralized collagen scaffolds for bone tissue engineering.. Bioact Mater 2021 May;6(5):1491-1511.
              doi: 10.1016/j.bioactmat.2020.11.004pubmed: 33294729google scholar: lookup
            11. Zamboulis DE, Thorpe CT, Ashraf Kharaz Y, Birch HL, Screen HR, Clegg PD. Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix.. Elife 2020 Oct 16;9.
              doi: 10.7554/eLife.58075pubmed: 33063662google scholar: lookup
            12. Eekhoff JD, Steenbock H, Berke IM, Brinckmann J, Yanagisawa H, Wagenseil JE, Lake SP. Dysregulated assembly of elastic fibers in fibulin-5 knockout mice results in a tendon-specific increase in elastic modulus.. J Mech Behav Biomed Mater 2021 Jan;113:104134.
              doi: 10.1016/j.jmbbm.2020.104134pubmed: 33045519google scholar: lookup
            13. Mersmann F, Laube G, Bohm S, Arampatzis A. Muscle and Tendon Morphology in Early-Adolescent Athletes and Untrained Peers.. Front Physiol 2020;11:1029.
              doi: 10.3389/fphys.2020.01029pubmed: 32973557google scholar: lookup
            14. Choi H, Simpson D, Wang D, Prescott M, Pitsillides AA, Dudhia J, Clegg PD, Ping P, Thorpe CT. Heterogeneity of proteome dynamics between connective tissue phases of adult tendon.. Elife 2020 May 12;9.
              doi: 10.7554/eLife.55262pubmed: 32393437google scholar: lookup
            15. Yin NH, Parker AW, Matousek P, Birch HL. Detection of Age-Related Changes in Tendon Molecular Composition by Raman Spectroscopy-Potential for Rapid, Non-Invasive Assessment of Susceptibility to Injury.. Int J Mol Sci 2020 Mar 20;21(6).
              doi: 10.3390/ijms21062150pubmed: 32245089google scholar: lookup
            16. Couppé C, Svensson RB, Josefsen CO, Kjeldgaard E, Magnusson SP. Ultrasound speckle tracking of Achilles tendon in individuals with unilateral tendinopathy: a pilot study.. Eur J Appl Physiol 2020 Mar;120(3):579-589.
              doi: 10.1007/s00421-020-04317-5pubmed: 32060739google scholar: lookup
            17. Chang J, Garva R, Pickard A, Yeung CC, Mallikarjun V, Swift J, Holmes DF, Calverley B, Lu Y, Adamson A, Raymond-Hayling H, Jensen O, Shearer T, Meng QJ, Kadler KE. Circadian control of the secretory pathway maintains collagen homeostasis.. Nat Cell Biol 2020 Jan;22(1):74-86.
              doi: 10.1038/s41556-019-0441-zpubmed: 31907414google scholar: lookup
            18. Muench JR, Thelen DG, Henak CR. Interfibrillar shear behavior is altered in aging tendon fascicles.. Biomech Model Mechanobiol 2020 Jun;19(3):841-849.
              doi: 10.1007/s10237-019-01251-0pubmed: 31707625google scholar: lookup
            19. Docking SI, Cook J. How do tendons adapt? Going beyond tissue responses to understand positive adaptation and pathology development: A narrative review.. J Musculoskelet Neuronal Interact 2019 Sep 1;19(3):300-310.
              pubmed: 31475937
            20. Sugiyama Y, Naito K, Goto K, Kojima Y, Furuhata A, Igarashi M, Nagaoka I, Kaneko K. Effect of aging on the tendon structure and tendon-associated gene expression in mouse foot flexor tendon.. Biomed Rep 2019 Apr;10(4):238-244.
              doi: 10.3892/br.2019.1200pubmed: 30972219google scholar: lookup
            21. Nagano T, Yamao S, Terachi A, Yarimizu H, Itoh H, Katasho R, Kawai K, Nakashima A, Iwasaki T, Kikkawa U, Kamada S. d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species.. Life Sci Alliance 2019 Feb;2(1).
              doi: 10.26508/lsa.201800045pubmed: 30659069google scholar: lookup
            22. Guzzoni V, Selistre-de-Araújo HS, Marqueti RC. Tendon Remodeling in Response to Resistance Training, Anabolic Androgenic Steroids and Aging.. Cells 2018 Dec 7;7(12).
              doi: 10.3390/cells7120251pubmed: 30544536google scholar: lookup
            23. Dang M, Saunders L, Niu X, Fan Y, Ma PX. Biomimetic delivery of signals for bone tissue engineering.. Bone Res 2018;6:25.
              doi: 10.1038/s41413-018-0025-8pubmed: 30181921google scholar: lookup
            24. Hudson DM, Archer M, King KB, Eyre DR. Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase-mediated cross-linking.. J Biol Chem 2018 Oct 5;293(40):15620-15627.
              doi: 10.1074/jbc.RA118.004829pubmed: 30143533google scholar: lookup
            25. Magnusson SP, Kjaer M. The impact of loading, unloading, ageing and injury on the human tendon.. J Physiol 2019 Mar;597(5):1283-1298.
              doi: 10.1113/JP275450pubmed: 29920664google scholar: lookup
            26. Quigley AS, Bancelin S, Deska-Gauthier D, Légaré F, Kreplak L, Veres SP. In tendons, differing physiological requirements lead to functionally distinct nanostructures.. Sci Rep 2018 Mar 13;8(1):4409.
              doi: 10.1038/s41598-018-22741-8pubmed: 29535366google scholar: lookup
            27. Kharaz YA, Canty-Laird EG, Tew SR, Comerford EJ. Variations in internal structure, composition and protein distribution between intra- and extra-articular knee ligaments and tendons.. J Anat 2018 Jun;232(6):943-955.
              doi: 10.1111/joa.12802pubmed: 29498035google scholar: lookup
            28. Pöschke A, Krähling B, Failing K, Staszyk C. Molecular Characteristics of the Equine Periodontal Ligament.. Front Vet Sci 2017;4:235.
              doi: 10.3389/fvets.2017.00235pubmed: 29376061google scholar: lookup
            29. Turlo AJ, Ashraf Kharaz Y, Clegg PD, Anderson J, Peffers MJ. Donor age affects proteome composition of tenocyte-derived engineered tendon.. BMC Biotechnol 2018 Jan 16;18(1):2.
              doi: 10.1186/s12896-018-0414-5pubmed: 29338716google scholar: lookup
            30. Collier TA, Nash A, Birch HL, de Leeuw NH. Effect on the mechanical properties of type I collagen of intra-molecular lysine-arginine derived advanced glycation end-product cross-linking.. J Biomech 2018 Jan 23;67:55-61.
              doi: 10.1016/j.jbiomech.2017.11.021pubmed: 29254633google scholar: lookup
            31. Mersmann F, Bohm S, Arampatzis A. Imbalances in the Development of Muscle and Tendon as Risk Factor for Tendinopathies in Youth Athletes: A Review of Current Evidence and Concepts of Prevention.. Front Physiol 2017;8:987.
              doi: 10.3389/fphys.2017.00987pubmed: 29249987google scholar: lookup
            32. Pease LI, Clegg PD, Proctor CJ, Shanley DJ, Cockell SJ, Peffers MJ. Cross platform analysis of transcriptomic data identifies ageing has distinct and opposite effects on tendon in males and females.. Sci Rep 2017 Oct 31;7(1):14443.
              doi: 10.1038/s41598-017-14650-zpubmed: 29089527google scholar: lookup
            33. Bechshøft CL, Schjerling P, Bornø A, Holm L. Existence of life-time stable proteins in mature rats-Dating of proteins' age by repeated short-term exposure to labeled amino acids throughout age.. PLoS One 2017;12(9):e0185605.
              doi: 10.1371/journal.pone.0185605pubmed: 28957442google scholar: lookup
            34. Gagliano N, Menon A, Cabitza F, Compagnoni R, Randelli P. Morphological and molecular characterization of human hamstrings shows that tendon features are not influenced by donor age.. Knee Surg Sports Traumatol Arthrosc 2018 Jan;26(1):343-352.
              doi: 10.1007/s00167-017-4661-0pubmed: 28770299google scholar: lookup
            35. Kadler KE. Fell Muir Lecture: Collagen fibril formation in vitro and in vivo.. Int J Exp Pathol 2017 Feb;98(1):4-16.
              doi: 10.1111/iep.12224pubmed: 28508516google scholar: lookup
            36. Ackerman JE, Bah I, Jonason JH, Buckley MR, Loiselle AE. Aging does not alter tendon mechanical properties during homeostasis, but does impair flexor tendon healing.. J Orthop Res 2017 Dec;35(12):2716-2724.
              doi: 10.1002/jor.23580pubmed: 28419543google scholar: lookup
            37. Skovgaard D, Svensson RB, Scheijen J, Eliasson P, Mogensen P, Hag AM, Kjær M, Schalkwijk CG, Schjerling P, Magnusson SP, Couppé C. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon.. Physiol Rep 2017 Mar;5(6).
              doi: 10.14814/phy2.13215pubmed: 28336820google scholar: lookup
            38. Dakin SG, Buckley CD, Al-Mossawi MH, Hedley R, Martinez FO, Wheway K, Watkins B, Carr AJ. Persistent stromal fibroblast activation is present in chronic tendinopathy.. Arthritis Res Ther 2017 Jan 25;19(1):16.
              doi: 10.1186/s13075-016-1218-4pubmed: 28122639google scholar: lookup
            39. Young SR, Gardiner B, Mehdizadeh A, Rubenson J, Umberger B, Smith DW. Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model.. PLoS Comput Biol 2016 Sep;12(9):e1005106.
              doi: 10.1371/journal.pcbi.1005106pubmed: 27684554google scholar: lookup
            40. Collier TA, Nash A, Birch HL, de Leeuw NH. Intra-molecular lysine-arginine derived advanced glycation end-product cross-linking in Type I collagen: A molecular dynamics simulation study.. Biophys Chem 2016 Nov;218:42-46.
              doi: 10.1016/j.bpc.2016.09.003pubmed: 27648753google scholar: lookup
            41. Cook JL, Rio E, Purdam CR, Docking SI. Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research?. Br J Sports Med 2016 Oct;50(19):1187-91.
              doi: 10.1136/bjsports-2015-095422pubmed: 27127294google scholar: lookup
            42. Thorpe CT, Karunaseelan KJ, Ng Chieng Hin J, Riley GP, Birch HL, Clegg PD, Screen HR. Distribution of proteins within different compartments of tendon varies according to tendon type.. J Anat 2016 Sep;229(3):450-8.
              doi: 10.1111/joa.12485pubmed: 27113131google scholar: lookup
            43. Thorpe CT, Peffers MJ, Simpson D, Halliwell E, Screen HR, Clegg PD. Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition.. Sci Rep 2016 Feb 4;6:20455.
              doi: 10.1038/srep20455pubmed: 26842662google scholar: lookup
            44. Salini V, Vanni D, Pantalone A, Abate M. Platelet Rich Plasma Therapy in Non-insertional Achilles Tendinopathy: The Efficacy is Reduced in 60-years Old People Compared to Young and Middle-Age Individuals.. Front Aging Neurosci 2015;7:228.
              doi: 10.3389/fnagi.2015.00228pubmed: 26696880google scholar: lookup
            45. Tempfer H, Traweger A. Tendon Vasculature in Health and Disease.. Front Physiol 2015;6:330.
              doi: 10.3389/fphys.2015.00330pubmed: 26635616google scholar: lookup
            46. Dyment NA, Galloway JL. Regenerative biology of tendon: mechanisms for renewal and repair.. Curr Mol Biol Rep 2015 Sep;1(3):124-131.
              doi: 10.1007/s40610-015-0021-3pubmed: 26389023google scholar: lookup
            47. Atesok K, Fu FH, Sekiya I, Stolzing A, Ochi M, Rodeo SA. Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential.. Knee Surg Sports Traumatol Arthrosc 2017 Feb;25(2):626-636.
              doi: 10.1007/s00167-015-3763-9pubmed: 26298714google scholar: lookup
            48. Beaulieu ML, Wojtys EM, Ashton-Miller JA. Risk of anterior cruciate ligament fatigue failure is increased by limited internal femoral rotation during in vitro repeated pivot landings.. Am J Sports Med 2015 Sep;43(9):2233-41.
              doi: 10.1177/0363546515589164pubmed: 26122384google scholar: lookup
            49. Collier TA, Nash A, Birch HL, de Leeuw NH. Preferential sites for intramolecular glucosepane cross-link formation in type I collagen: A thermodynamic study.. Matrix Biol 2015 Oct;48:78-88.
              doi: 10.1016/j.matbio.2015.06.001pubmed: 26049074google scholar: lookup
            50. Thorpe CT, Godinho MSC, Riley GP, Birch HL, Clegg PD, Screen HRC. The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons.. J Mech Behav Biomed Mater 2015 Dec;52:85-94.
              doi: 10.1016/j.jmbbm.2015.04.009pubmed: 25958330google scholar: lookup
            51. Peffers MJ, Fang Y, Cheung K, Wei TK, Clegg PD, Birch HL. Transcriptome analysis of ageing in uninjured human Achilles tendon.. Arthritis Res Ther 2015 Feb 18;17(1):33.
              doi: 10.1186/s13075-015-0544-2pubmed: 25888722google scholar: lookup
            52. Spiesz EM, Thorpe CT, Chaudhry S, Riley GP, Birch HL, Clegg PD, Screen HR. Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise.. J Orthop Res 2015 Jun;33(6):889-97.
              doi: 10.1002/jor.22879pubmed: 25721513google scholar: lookup
            53. Screen HR, Berk DE, Kadler KE, Ramirez F, Young MF. Tendon functional extracellular matrix.. J Orthop Res 2015 Jun;33(6):793-9.
              doi: 10.1002/jor.22818pubmed: 25640030google scholar: lookup
            54. Frizziero A, Vittadini F, Gasparre G, Masiero S. Impact of oestrogen deficiency and aging on tendon: concise review.. Muscles Ligaments Tendons J 2014 Jul;4(3):324-8.
              pubmed: 25489550
            55. Tempfer H, Kaser-Eichberger A, Korntner S, Lehner C, Kunkel N, Traweger A, Trost A, Strohmaier C, Bogner B, Runge C, Bruckner D, Krefft K, Heindl LM, Reitsamer HA, Schrödl F. Presence of lymphatics in a rat tendon lesion model.. Histochem Cell Biol 2015 Apr;143(4):411-9.
              doi: 10.1007/s00418-014-1287-xpubmed: 25371325google scholar: lookup
            56. Peffers MJ, Thorpe CT, Collins JA, Eong R, Wei TK, Screen HR, Clegg PD. Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.. J Biol Chem 2014 Sep 12;289(37):25867-78.
              doi: 10.1074/jbc.M114.566554pubmed: 25077967google scholar: lookup
            57. Couppé C, Svensson RB, Grosset JF, Kovanen V, Nielsen RH, Olsen MR, Larsen JO, Praet SF, Skovgaard D, Hansen M, Aagaard P, Kjaer M, Magnusson SP. Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue.. Age (Dordr) 2014;36(4):9665.
              doi: 10.1007/s11357-014-9665-9pubmed: 24997017google scholar: lookup
            58. Wood LK, Kayupov E, Gumucio JP, Mendias CL, Claflin DR, Brooks SV. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice.. J Appl Physiol (1985) 2014 Aug 15;117(4):363-9.
              doi: 10.1152/japplphysiol.00256.2014pubmed: 24994884google scholar: lookup
            59. Zhou B, Zhou Y, Tang K. An overview of structure, mechanical properties, and treatment for age-related tendinopathy.. J Nutr Health Aging 2014 Apr;18(4):441-8.
              doi: 10.1007/s12603-014-0026-2pubmed: 24676328google scholar: lookup
            60. Thorpe CT, Riley GP, Birch HL, Clegg PD, Screen HR. Fascicles from energy-storing tendons show an age-specific response to cyclic fatigue loading.. J R Soc Interface 2014 Mar 6;11(92):20131058.
              doi: 10.1098/rsif.2013.1058pubmed: 24402919google scholar: lookup
            61. Dakin SG, Smith RK, Heinegård D, Önnerfjord P, Khabut A, Dudhia J. Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein).. J Biol Chem 2014 Feb 21;289(8):4919-27.
              doi: 10.1074/jbc.M113.511972pubmed: 24398684google scholar: lookup
            62. Birch HL, Thorpe CT, Rumian AP. Specialisation of extracellular matrix for function in tendons and ligaments.. Muscles Ligaments Tendons J 2013 Jan;3(1):12-22.
              doi: 10.11138/mltj/2013.3.1.012pubmed: 23885341google scholar: lookup
            63. Svensson RB, Mulder H, Kovanen V, Magnusson SP. Fracture mechanics of collagen fibrils: influence of natural cross-links.. Biophys J 2013 Jun 4;104(11):2476-84.
              doi: 10.1016/j.bpj.2013.04.033pubmed: 23746520google scholar: lookup
            64. Thorpe CT, Birch HL, Clegg PD, Screen HR. The role of the non-collagenous matrix in tendon function.. Int J Exp Pathol 2013 Aug;94(4):248-59.
              doi: 10.1111/iep.12027pubmed: 23718692google scholar: lookup
            65. Heinemeier KM, Schjerling P, Heinemeier J, Magnusson SP, Kjaer M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C.. FASEB J 2013 May;27(5):2074-9.
              doi: 10.1096/fj.12-225599pubmed: 23401563google scholar: lookup
            66. Kostrominova TY, Brooks SV. Age-related changes in structure and extracellular matrix protein expression levels in rat tendons.. Age (Dordr) 2013 Dec;35(6):2203-14.
              doi: 10.1007/s11357-013-9514-2pubmed: 23354684google scholar: lookup
            67. Torricelli P, Veronesi F, Pagani S, Maffulli N, Masiero S, Frizziero A, Fini M. In vitro tenocyte metabolism in aging and oestrogen deficiency.. Age (Dordr) 2013 Dec;35(6):2125-36.
              doi: 10.1007/s11357-012-9500-0pubmed: 23274854google scholar: lookup
            68. Thorpe CT, Udeze CP, Birch HL, Clegg PD, Screen HR. Specialization of tendon mechanical properties results from interfascicular differences.. J R Soc Interface 2012 Nov 7;9(76):3108-17.
              doi: 10.1098/rsif.2012.0362pubmed: 22764132google scholar: lookup
            69. Corps AN, Robinson AH, Harrall RL, Avery NC, Curry VA, Hazleman BL, Riley GP. Changes in matrix protein biochemistry and the expression of mRNA encoding matrix proteins and metalloproteinases in posterior tibialis tendinopathy.. Ann Rheum Dis 2012 May;71(5):746-52.
              doi: 10.1136/annrheumdis-2011-200391pubmed: 22241901google scholar: lookup
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