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Aging cell2007; 6(4); 547-556; doi: 10.1111/j.1474-9726.2007.00307.x

Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity.

Abstract: Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collide in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1 Hz for 24 h) on tissue mechanical properties, loss of ECM protein and matrix metalloproteinase (MMP) expression. We show significantly diminished mechanical strength of cyclically loaded tissue compared to controls (39.7 +/- 12%, P <or= 0.05) this reduction was dependent on the presence of both viable cells and metalloproteinase activity. Furthermore, tendon from older specimens was more susceptible to weakening (11-30 years, 50%P <or= 0.05) compared to immature and young mature tissue (1-3 years, 34%; 4-10 years, 35%, respectively). Cyclical load also induced release of degraded cartilage oligomeric matrix protein, an integral ECM protein, an effect that could be mimicked by culture with fibronectin fragments. These findings indicate prolonged cyclical loading of physiological magnitude decreases tendon tensile strength by an active process, and that MMPs may contribute to loss of functional competence, exaggerated by age, via load-induced proteolytic disruption of the ECM.
Publication Date: 2007-06-18 PubMed ID: 17578513DOI: 10.1111/j.1474-9726.2007.00307.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

This research investigates how aging affects tendon strength, especially when tendons endure repeated mechanical stress. The study finds that active cell activities and the functioning of enzymes called matrix metalloproteinases play significant roles in age-related tendon weakening.

Understanding Tendons and Their Functioning

  • Tendons are important tissues that connect muscles to bones and are essential to movement.
  • The functional efficiency of tendons depends on their extracellular matrix (ECM), an ordered structure that provides tensile strength, enabling tendons to withstand loads.
  • As people age, tendons often lose their functional efficiency due to subtle and cumulative changes to the ECM.
  • An increase in age and physical activity often leads to tendinopathies – conditions where tendons become painful or damage due to overuse.

Research Hypothesis and Methodology

  • The researchers hypothesized that aged tendons might fail due to cumulative damage arising from a combination of diminished matrix repair and fragmentation of ECM proteins, induced by prolonged cyclical loading.
  • The researchers developed an equine tendon explant model to study the effects of aging on the influence of prolonged cyclical loading at physiologically relevant strain rates on tissue mechanical properties, and ECM protein and matrix metalloproteinase (MMP) expression.

Key Findings of the Study

  • The results showed that the mechanical strength of tissues undergoing cyclical loading was significantly diminished compared to control tissues, and this reduction in strength was dependent on the presence of viable cells and metalloproteinase activity.
  • Tissue from older specimens was found to be more susceptible to weakening than relatively younger tissues.
  • Cyclical load also induced the release of degraded cartilage oligomeric matrix protein (an integral ECM protein), an effect that was reproduced by culture with fibronectin fragments.

Conclusions and Implications from the Study

  • The findings indicate that prolonged cyclical loading of physiological magnitude decreases tendon tensile strength via an active process.
  • MMPs may also contribute to the loss of functional competence, a problem that could be exacerbated by aging, through the load-induced proteolytic disruption of the ECM.
  • These findings suggest that preventing this process or countering its effects might form a useful strategy in managing certain age- and exercise-related tendon diseases.

Cite This Article

APA
Dudhia J, Scott CM, Draper ER, Heinegård D, Pitsillides AA, Smith RK. (2007). Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell, 6(4), 547-556. https://doi.org/10.1111/j.1474-9726.2007.00307.x

Publication

ISSN: 1474-9718
NlmUniqueID: 101130839
Country: England
Language: English
Volume: 6
Issue: 4
Pages: 547-556

Researcher Affiliations

Dudhia, Jayesh
  • Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK. jdudhia@rvc.ac.uk
Scott, Charlotte M
    Draper, Edward R C
      Heinegård, Dick
        Pitsillides, Andrew A
          Smith, Roger K

            MeSH Terms

            • Aging / physiology
            • Animals
            • Extracellular Matrix / metabolism
            • Horses
            • Matrix Metalloproteinases / metabolism
            • Motor Activity
            • Muscle, Skeletal
            • Stress, Mechanical
            • Tendinopathy
            • Tendons / enzymology
            • Tendons / physiology
            • Tensile Strength

            Citations

            This article has been cited 49 times.
            1. Li ZJ, Yang QQ, Zhou YL. Biological and Mechanical Factors and Epigenetic Regulation Involved in Tendon Healing.. Stem Cells Int 2023;2023:4387630.
              doi: 10.1155/2023/4387630pubmed: 36655033google scholar: lookup
            2. Korcari A, Przybelski SJ, Gingery A, Loiselle AE. Impact of aging on tendon homeostasis, tendinopathy development, and impaired healing.. Connect Tissue Res 2023 Jan;64(1):1-13.
              doi: 10.1080/03008207.2022.2102004pubmed: 35903886google scholar: lookup
            3. Ribbans WJ, September AV, Collins M. Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review.. Life (Basel) 2022 Apr 29;12(5).
              doi: 10.3390/life12050663pubmed: 35629331google scholar: lookup
            4. 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
            5. Lu V, Tennyson M, Zhang J, Khan W. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair-A Systematic Review of In Vivo Studies.. Cells 2021 Sep 27;10(10).
              doi: 10.3390/cells10102553pubmed: 34685532google scholar: lookup
            6. Liu Q, Zhu Y, Zhu W, Zhang G, Yang YP, Zhao C. The role of MicroRNAs in tendon injury, repair, and related tissue engineering.. Biomaterials 2021 Oct;277:121083.
            7. Mok TN, Chen J, Pan J, Ming WK, He Q, Sin TH, Deng J, Li J, Zha Z. Use of a Virtual Reality Simulator for Tendon Repair Training: Randomized Controlled Trial.. JMIR Serious Games 2021 Jul 12;9(3):e27544.
              doi: 10.2196/27544pubmed: 34255649google scholar: lookup
            8. Oreff GL, Fenu M, Vogl C, Ribitsch I, Jenner F. Species variations in tenocytes' response to inflammation require careful selection of animal models for tendon research.. Sci Rep 2021 Jun 14;11(1):12451.
              doi: 10.1038/s41598-021-91914-9pubmed: 34127759google scholar: lookup
            9. Meeremans M, Van de Walle GR, Van Vlierberghe S, De Schauwer C. The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research.. Front Cell Dev Biol 2021;9:651164.
              doi: 10.3389/fcell.2021.651164pubmed: 34012963google scholar: lookup
            10. Bajpai A, Li R, Chen W. The cellular mechanobiology of aging: from biology to mechanics.. Ann N Y Acad Sci 2021 May;1491(1):3-24.
              doi: 10.1111/nyas.14529pubmed: 33231326google scholar: lookup
            11. Riasat K, Bardell D, Goljanek-Whysall K, Clegg PD, Peffers MJ. Epigenetic mechanisms in Tendon Ageing.. Br Med Bull 2020 Oct 14;135(1):90-107.
              doi: 10.1093/bmb/ldaa023pubmed: 32827252google scholar: lookup
            12. Neph A, Schroeder A, Enseki KR, Everts PA, Wang JH, Onishi K. Role of Mechanical Loading for Platelet-Rich Plasma-Treated Achilles Tendinopathy.. Curr Sports Med Rep 2020 Jun;19(6):209-216.
              doi: 10.1249/JSR.0000000000000719pubmed: 32516191google scholar: lookup
            13. Lui PPY, Wong CM. Biology of Tendon Stem Cells and Tendon in Aging.. Front Genet 2019;10:1338.
              doi: 10.3389/fgene.2019.01338pubmed: 32010194google scholar: lookup
            14. 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
            15. Zuskov A, Freedman BR, Gordon JA, Sarver JJ, Buckley MR, Soslowsky LJ. Tendon Biomechanics and Crimp Properties Following Fatigue Loading Are Influenced by Tendon Type and Age in Mice.. J Orthop Res 2020 Jan;38(1):36-42.
              doi: 10.1002/jor.24407pubmed: 31286548google scholar: lookup
            16. McBeath R, Edwards RW, O'Hara BJ, Maltenfort MG, Parks SM, Steplewski A, Osterman AL, Shapiro IM. Tendinosis develops from age- and oxygen tension-dependent modulation of Rac1 activity.. Aging Cell 2019 Jun;18(3):e12934.
              doi: 10.1111/acel.12934pubmed: 30938056google scholar: lookup
            17. Dakin SG, Colas RA, Newton J, Gwilym S, Jones N, Reid HAB, Wood S, Appleton L, Wheway K, Watkins B, Dalli J, Carr AJ. 15-Epi-LXA(4) and MaR1 counter inflammation in stromal cells from patients with Achilles tendinopathy and rupture.. FASEB J 2019 Jul;33(7):8043-8054.
              doi: 10.1096/fj.201900196Rpubmed: 30916999google scholar: lookup
            18. Freedman BR, Mooney DJ. Biomaterials to Mimic and Heal Connective Tissues.. Adv Mater 2019 May;31(19):e1806695.
              doi: 10.1002/adma.201806695pubmed: 30908806google scholar: lookup
            19. Ueda Y, Inui A, Mifune Y, Takase F, Kataoka T, Kurosawa T, Yamaura K, Kokubu T, Kuroda R. Molecular changes to tendons after collagenase-induced acute tendon injury in a senescence-accelerated mouse model.. BMC Musculoskelet Disord 2019 Mar 21;20(1):120.
              doi: 10.1186/s12891-019-2488-1pubmed: 30902076google scholar: lookup
            20. 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
            21. Connizzo BK, Grodzinsky AJ. Release of pro-inflammatory cytokines from muscle and bone causes tenocyte death in a novel rotator cuff in vitro explant culture model.. Connect Tissue Res 2018 Sep;59(5):423-436.
              doi: 10.1080/03008207.2018.1439486pubmed: 29447021google scholar: lookup
            22. 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
            23. Dakin SG, Newton J, Martinez FO, Hedley R, Gwilym S, Jones N, Reid HAB, Wood S, Wells G, Appleton L, Wheway K, Watkins B, Carr AJ. Chronic inflammation is a feature of Achilles tendinopathy and rupture.. Br J Sports Med 2018 Mar;52(6):359-367.
              doi: 10.1136/bjsports-2017-098161pubmed: 29118051google scholar: lookup
            24. Dakin SG. MicroRNA Replacement: A New Era of Molecular Therapy for Tendon Disorders?. Mol Ther 2017 Oct 4;25(10):2243-2244.
              doi: 10.1016/j.ymthe.2017.09.004pubmed: 28939087google scholar: lookup
            25. Pardes AM, Beach ZM, Raja H, Rodriguez AB, Freedman BR, Soslowsky LJ. Aging leads to inferior Achilles tendon mechanics and altered ankle function in rodents.. J Biomech 2017 Jul 26;60:30-38.
            26. Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.. Stem Cell Res Ther 2017 Jun 5;8(1):129.
              doi: 10.1186/s13287-017-0564-8pubmed: 28583184google scholar: lookup
            27. 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
            28. Zhang J, Yuan T, Wang JH. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats.. Oncotarget 2016 Feb 23;7(8):8498-512.
              doi: 10.18632/oncotarget.7381pubmed: 26885754google scholar: lookup
            29. Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJ, Smith RD, Wheway K, Watkins B, Roche L, Carr AJ. Inflammation activation and resolution in human tendon disease.. Sci Transl Med 2015 Oct 28;7(311):311ra173.
              doi: 10.1126/scitranslmed.aac4269pubmed: 26511510google scholar: lookup
            30. 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
            31. 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
            32. 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
            33. Poulet B, de Souza R, Knights CB, Gentry C, Wilson AM, Bevan S, Chang YM, Pitsillides AA. Modifications of gait as predictors of natural osteoarthritis progression in STR/Ort mice.. Arthritis Rheumatol 2014 Jul;66(7):1832-42.
              doi: 10.1002/art.38616pubmed: 24623711google scholar: lookup
            34. Dakin SG, Dudhia J, Smith RK. Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):121-7.
              doi: 10.1016/j.vetimm.2014.01.007pubmed: 24556326google scholar: lookup
            35. 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
            36. Piróg KA, Katakura Y, Mironov A, Briggs MD. Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases.. PLoS One 2013;8(11):e82412.
              doi: 10.1371/journal.pone.0082412pubmed: 24312420google scholar: lookup
            37. Gransee HM, Mantilla CB, Sieck GC. Respiratory muscle plasticity.. Compr Physiol 2012 Apr;2(2):1441-62.
              doi: 10.1002/cphy.c110050pubmed: 23798306google scholar: lookup
            38. Asadollahi S, Keith PP. Flexor tendon injuries following plate fixation of distal radius fractures: a systematic review of the literature.. J Orthop Traumatol 2013 Dec;14(4):227-34.
              doi: 10.1007/s10195-013-0245-zpubmed: 23670492google scholar: lookup
            39. Dean BJ, Franklin SL, Carr AJ. A systematic review of the histological and molecular changes in rotator cuff disease.. Bone Joint Res 2012 Jul;1(7):158-66.
              doi: 10.1302/2046-3758.17.2000115pubmed: 23610686google scholar: lookup
            40. Yu TY, Pang JH, Wu KP, Chen MJ, Chen CH, Tsai WC. Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes.. BMC Musculoskelet Disord 2013 Jan 2;14:2.
              doi: 10.1186/1471-2474-14-2pubmed: 23281803google scholar: lookup
            41. 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
            42. Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.. PLoS One 2012;7(11):e48978.
              doi: 10.1371/journal.pone.0048978pubmed: 23155437google scholar: lookup
            43. Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J. Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.. PLoS One 2012;7(2):e32333.
              doi: 10.1371/journal.pone.0032333pubmed: 22384219google scholar: lookup
            44. Abraham T, Fong G, Scott A. Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading.. BMC Musculoskelet Disord 2011 Jan 26;12:26.
              doi: 10.1186/1471-2474-12-26pubmed: 21269488google scholar: lookup
            45. Lakemeier S, Braun J, Efe T, Foelsch C, Archontidou-Aprin E, Fuchs-Winkelmann S, Paletta JR, Schofer MD. Expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff.. Knee Surg Sports Traumatol Arthrosc 2011 Oct;19(10):1760-5.
              doi: 10.1007/s00167-010-1367-ypubmed: 21222105google scholar: lookup
            46. Fu SC, Rolf C, Cheuk YC, Lui PP, Chan KM. Deciphering the pathogenesis of tendinopathy: a three-stages process.. Sports Med Arthrosc Rehabil Ther Technol 2010 Dec 13;2:30.
              doi: 10.1186/1758-2555-2-30pubmed: 21144004google scholar: lookup
            47. Tajana MS, Murena L, Valli F, Passi A, Grassi FA. Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease.. Chir Organi Mov 2009 Apr;93 Suppl 1:S41-8.
              doi: 10.1007/s12306-009-0004-8pubmed: 19711169google scholar: lookup
            48. Ensey JS, Hollander MS, Wu JZ, Kashon ML, Baker BB, Cutlip RG. Response of tibialis anterior tendon to a chronic exposure of stretch-shortening cycles: age effects.. Biomed Eng Online 2009 Jun 29;8:12.
              doi: 10.1186/1475-925X-8-12pubmed: 19563638google scholar: lookup
            49. Korecki CL, Kuo CK, Tuan RS, Iatridis JC. Intervertebral disc cell response to dynamic compression is age and frequency dependent.. J Orthop Res 2009 Jun;27(6):800-6.
              doi: 10.1002/jor.20814pubmed: 19058142google scholar: lookup