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Journal of anatomy2007; 211(3); 325-334; doi: 10.1111/j.1469-7580.2007.00781.x

Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons.

Abstract: Injury to the energy-storing superficial digital flexor tendon is common in equine athletes and is age-related. Tenocytes in the superficial digital flexor tendon of adult horses appear to have limited ability to respond adaptively to exercise or prevent the accumulation of strain-induced microdamage. It has been suggested that conditioning exercise should be introduced during the growth period, when tenocytes may be more responsive to increased quantities or intensities of mechanical strain. Tenocytes are linked into networks by gap junctions that allow coordination of synthetic activity and facilitate strain-induced collagen synthesis. We hypothesised that there are reductions in cellular expression of the gap junction proteins connexin (Cx) 43 and 32 during maturation and ageing of the superficial digital flexor tendon that do not occur in the non-injury-prone common digital extensor tendon. Cryosections from the superficial digital flexor tendon and common digital extensor tendon of 5 fetuses, 5 foals (1-6 months), 5 young adults (2-7 years) and 5 old horses (18-33 years) were immunofluorescently labelled and quantitative confocal laser microscopy was performed. Expression of Cx43 and Cx32 protein per tenocyte was significantly higher in the fetal group compared with all other age groups in both tendons. The density of tenocytes was found to be highest in immature tissue. Higher levels of cellularity and connexin protein expression in immature tendons are likely to relate to requirements for tissue remodelling and growth. However, if further studies demonstrate that this correlates with greater gap junctional communication efficiency and synthetic responsiveness to mechanical strain in immature compared with adult tendons, it could support the concept of early introduction of controlled exercise as a means of increasing resistance to later injury.
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Publication Date: 2007-09-13 PubMed ID: 17848160PubMed Central: PMC2375813DOI: 10.1111/j.1469-7580.2007.00781.xGoogle Scholar: Lookup
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  • Comparative Study
  • Journal Article

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 the role of gap junction proteins in the tendons of horses, and their change during maturation and ageing. Findings suggest that the proteins, connexin 43 and 32, are significantly more abundant in fetal tissues, implying that controlled exercise introduced early may help increase resistance to injury later in life.

Understanding the Research

The research was driven by the observation that equine athlete injuries are common and often linked to age. These injuries often involve the energy-storing superficial digital flexor tendon. Adult horse tenocytes – the cells found in tendons and ligaments – seem to have a limited ability to adapt and prevent strain-induced damage. Early conditioning exercise may increase their responsiveness.

  • The research tested the hypothesis that the decrease in connexin 43 and 32 gap junction proteins – which have a role in coordinating synthetic activity and strain-induced collagen synthesis among tenocytes – will not occur in an injury-resistant tendon (common digital extensor tendon) but would be seen in the superficial digital flexor tendon as it matures and ages.
  • The comparison of these proteins’ expression was done using tissue samples from the tendons of fetuses, foals (1-6 months old), young adult (2-7 years old), and old horses (18-33 years old). The study used immunofluorescent labeling and quantitative confocal laser microscopy for this purpose.

Key Findings

  • The research found that the expression of connexin 43 and 32 per tenocyte was significantly higher in the fetal stage than all the other age groups studied, regardless of tendon type.
  • The density of tenocytes in immature tissue was found to be the highest, indicating higher cellularity and protein expression at this stage for tissue remodelling and growth.
  • This leads to the possibility that increased gap junctional communication and synthetic responsiveness to mechanical strain at the immature stage compared to adult tendons could explain the reduced injury resistance in adults.

Significance and Future Implications

  • The study sheds light on the importance of gap junction proteins in maintaining the health of equine tendons.
  • The maturity-dependent decrease in these proteins can partially explain the higher susceptibility of adult horses to tendon injuries.
  • If further research supports these findings, it could validate the idea of introducing controlled exercise at an early stage of horse development, thereby improving their injury resistance later in life.

Cite This Article

APA
Stanley RL, Fleck RA, Becker DL, Goodship AE, Ralphs JR, Patterson-Kane JC. (2007). Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons. J Anat, 211(3), 325-334. https://doi.org/10.1111/j.1469-7580.2007.00781.x

Publication

Journal of anatomy
ISSN: 0021-8782
NlmUniqueID: 0137162
Country: England
Language: English
Volume: 211
Issue: 3
Pages: 325-334

Researcher Affiliations

Stanley, Rachael L
  • Department of Pathology and Infectious Diseases, Royal Veterinary College, Hatfield, Hertfordshire, UK. rstanley@rvc.ac.uk
Fleck, Roland A
    Becker, David L
      Goodship, Allen E
        Ralphs, Jim R
          Patterson-Kane, Janet C

            MeSH Terms

            • Aging / physiology
            • Animals
            • Cell Count
            • Connexin 43 / analysis
            • Connexins / analysis
            • Fluorescent Antibody Technique
            • Forelimb
            • Horses / physiology
            • Microscopy, Confocal
            • Physical Conditioning, Animal
            • Stress, Mechanical
            • Tendons / cytology
            • Tendons / growth & development
            • Tendons / metabolism

            Grant Funding

            • BB/D524883/1 / Biotechnology and Biological Sciences Research Council

            References

            This article includes 57 references
            1. Andrade-Rozental AF, Rozental R, Hopperstad MG, Wu JK, Vrionis FD, Spray DC. Gap junctions: the "kiss of death" and the "kiss of life".. Brain Res Brain Res Rev 2000 Apr;32(1):308-15.
              pubmed: 10751679doi: 10.1016/s0165-0173(99)00099-5google scholar: lookup
            2. Arita K, Akiyama M, Tsuji Y, McMillan JR, Eady RA, Shimizu H. Changes in gap junction distribution and connexin expression pattern during human fetal skin development.. J Histochem Cytochem 2002 Nov;50(11):1493-500.
              pubmed: 12417615doi: 10.1177/002215540205001109google scholar: lookup
            3. Banes AJ, Tsuzaki M, Yamamoto J. Connexin expression is upregulated by mechanical load in avian and human tendon cells. Trans Orthop Res Soc Vol. 21. Atlanta: 1996. pp. 3–1.
            4. Banes AJ, Weinhold P, Yang X, Tsuzaki M, Bynum D, Bottlang M, Brown T. Gap junctions regulate responses of tendon cells ex vivo to mechanical loading.. Clin Orthop Relat Res 1999 Oct;(367 Suppl):S356-70.
              pubmed: 10546659doi: 10.1097/00003086-199910001-00034google scholar: lookup
            5. Batson EL, Paramour RJ, Smith TJ, Birch HL, Patterson-Kane JC, Goodship AE. Are the material properties and matrix composition of equine flexor and extensor tendons determined by their functions?. Equine Vet J 2003 May;35(3):314-8.
              pubmed: 12755437doi: 10.2746/042516403776148327google scholar: lookup
            6. Becker DL, Mobbs P. Connexin alpha1 and cell proliferation in the developing chick retina.. Exp Neurol 1999 Apr;156(2):326-32.
              pubmed: 10328939doi: 10.1006/exnr.1999.7027google scholar: lookup
            7. Beyer EC, Berthoud VM. Gap junction synthesis and degradation as therapeutic targets.. Curr Drug Targets 2002 Dec;3(6):409-16.
              pubmed: 12448693doi: 10.2174/1389450023347245google scholar: lookup
            8. Beyer EC, Paul DL, Goodenough DA. Connexin43: a protein from rat heart homologous to a gap junction protein from liver.. J Cell Biol 1987 Dec;105(6 Pt 1):2621-9.
              pmc: PMC2114703pubmed: 2826492doi: 10.1083/jcb.105.6.2621google scholar: lookup
            9. 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
            10. 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
            11. Brink PR. Are gap junction channels a therapeutic target and if so what properties are best exploited?. Curr Drug Targets 2002 Dec;3(6):417-25.
              pubmed: 12448694doi: 10.2174/1389450023347326google scholar: lookup
            12. Bullimore SR, Burn JF. Dynamically similar locomotion in horses.. J Exp Biol 2006 Feb;209(Pt 3):455-65.
              pubmed: 16424095doi: 10.1242/jeb.02029google scholar: lookup
            13. Cotrina ML, Gao Q, Lin JH, Nedergaard M. Expression and function of astrocytic gap junctions in aging.. Brain Res 2001 May 18;901(1-2):55-61.
              pubmed: 11368950doi: 10.1016/s0006-8993(01)02258-2google scholar: lookup
            14. Crevier-Denoix N, Collobert C, Sanaa M, Bernard N, Joly C, Pourcelot P, Geiger D, Bortolussi C, Bousseau B, Denoix JM. Mechanical correlations derived from segmental histologic study of the equine superficial digital flexor tendon, from foal to adult.. Am J Vet Res 1998 Aug;59(8):969-77.
              pubmed: 9706200
            15. Cusato K, Bosco A, Rozental R, Guimarães CA, Reese BE, Linden R, Spray DC. Gap junctions mediate bystander cell death in developing retina.. J Neurosci 2003 Jul 23;23(16):6413-22.
              pmc: PMC6740641pubmed: 12878681doi: 10.1523/jneurosci.23-16-06413.2003google scholar: lookup
            16. Elfgang C, Eckert R, Lichtenberg-Fraté H, Butterweck A, Traub O, Klein RA, Hülser DF, Willecke K. Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells.. J Cell Biol 1995 May;129(3):805-17.
              pmc: PMC2120441pubmed: 7537274doi: 10.1083/jcb.129.3.805google scholar: lookup
            17. Falk MM. Biosynthesis and structural composition of gap junction intercellular membrane channels.. Eur J Cell Biol 2000 Aug;79(8):564-74.
              pubmed: 11001493doi: 10.1078/0171-9335-00080google scholar: lookup
            18. Firth EC. The response of bone, articular cartilage and tendon to exercise in the horse.. J Anat 2006 Apr;208(4):513-26.
              pmc: PMC2100207pubmed: 16637875doi: 10.1111/j.1469-7580.2006.00547.xgoogle scholar: lookup
            19. Forge A, Becker D, Casalotti S, Edwards J, Evans WH, Lench N, Souter M. Gap junctions and connexin expression in the inner ear.. Novartis Found Symp 1999;219:134-50; discussion 151-6.
              pubmed: 10207902doi: 10.1002/9780470515587.ch9google scholar: lookup
            20. Gaietta G, Deerinck TJ, Adams SR, Bouwer J, Tour O, Laird DW, Sosinsky GE, Tsien RY, Ellisman MH. Multicolor and electron microscopic imaging of connexin trafficking.. Science 2002 Apr 19;296(5567):503-7.
              pubmed: 11964472doi: 10.1126/science.1068793google scholar: lookup
            21. Goldberg GS, Lampe PD, Nicholson BJ. Selective transfer of endogenous metabolites through gap junctions composed of different connexins.. Nat Cell Biol 1999 Nov;1(7):457-9.
              pubmed: 10559992doi: 10.1038/15693google scholar: lookup
            22. Goodenough DA, Paul DL. Beyond the gap: functions of unpaired connexon channels.. Nat Rev Mol Cell Biol 2003 Apr;4(4):285-94.
              pubmed: 12671651doi: 10.1038/nrm1072google scholar: lookup
            23. Goodman SA, May SA, Heinegård D, Smith RK. Tenocyte response to cyclical strain and transforming growth factor beta is dependent upon age and site of origin.. Biorheology 2004;41(5):613-28.
              pubmed: 15477668
            24. Goodship AE, Birch HL, Wilson AM. The pathobiology and repair of tendon and ligament injury.. Vet Clin North Am Equine Pract 1994 Aug;10(2):323-49.
              pubmed: 7987721doi: 10.1016/s0749-0739(17)30359-0google scholar: lookup
            25. Hintz HF, Hintz RL, Van Vleck LD. Growth rate of thoroughbreds, effect of age of dam, year and month of birth, and sex of foal.. J Anim Sci 1979 Mar;48(3):480-7.
              pubmed: 575130doi: 10.2527/jas1979.483480xgoogle scholar: lookup
            26. Hosaka Y, Teraoka H, Yamamoto E, Ueda H, Takehana K. Mechanism of cell death in inflamed superficial digital flexor tendon in the horse.. J Comp Pathol 2005 Jan;132(1):51-8.
              pubmed: 15629479doi: 10.1016/j.jcpa.2004.06.006google scholar: lookup
            27. Järvinen TA, Järvinen TL, Kannus P, Józsa L, Järvinen M. Collagen fibres of the spontaneously ruptured human tendons display decreased thickness and crimp angle.. J Orthop Res 2004 Nov;22(6):1303-9.
              pubmed: 15475213doi: 10.1016/j.orthres.2004.04.003google scholar: lookup
            28. Kannus P, Józsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients.. J Bone Joint Surg Am 1991 Dec;73(10):1507-25.
              pubmed: 1748700
            29. Kasashima Y, Smith RK, Birch HL, Takahashi T, Kusano K, Goodship AE. Exercise-induced tendon hypertrophy: cross-sectional area changes during growth are influenced by exercise.. Equine Vet J Suppl 2002 Sep;(34):264-8.
              pubmed: 12405698doi: 10.1111/j.2042-3306.2002.tb05430.xgoogle scholar: lookup
            30. Kear M, Smith RN. A method for recording tendon strain in sheep during locomotion.. Acta Orthop Scand 1975 Dec;46(6):896-905.
              pubmed: 1211126doi: 10.3109/17453677508989277google scholar: lookup
            31. 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
            32. Koterba AM. Physical examination. Equine clinical neonatology Baltimore: Lippincott Williams & Wilkins; 1990. pp. 71–79.
            33. Lauf U, Giepmans BN, Lopez P, Braconnot S, Chen SC, Falk MM. Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells.. Proc Natl Acad Sci U S A 2002 Aug 6;99(16):10446-51.
              pmc: PMC124935pubmed: 12149451doi: 10.1073/pnas.162055899google scholar: lookup
            34. Lin YL, Brama PA, Kiers GH, DeGroot J, van Weeren PR. Functional adaptation through changes in regional biochemical characteristics during maturation of equine superficial digital flexor tendons.. Am J Vet Res 2005 Sep;66(9):1623-9.
              pubmed: 16261838doi: 10.2460/ajvr.2005.66.1623google scholar: lookup
            35. Maffulli N, Ewen SW, Waterston SW, Reaper J, Barrass V. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing.. Am J Sports Med 2000 Jul-Aug;28(4):499-505.
              pubmed: 10921640doi: 10.1177/03635465000280040901google scholar: lookup
            36. McIlwraith CW. Diseases of the joints, tendons, ligaments and related structures. Adams’ lameness in horses 5. Philadelphia: Lippincott Williams & Wilkins; 2002. pp. 594–640.
            37. McNeilly CM, Banes AJ, Benjamin M, Ralphs JR. Tendon cells in vivo form a three dimensional network of cell processes linked by gap junctions.. J Anat 1996 Dec;189 ( Pt 3)(Pt 3):593-600.
              pmc: PMC1167702pubmed: 8982835
            38. Merrilees MJ, Flint MH. Ultrastructural study of tension and pressure zones in a rabbit flexor tendon.. Am J Anat 1980 Jan;157(1):87-106.
              pubmed: 7190773doi: 10.1002/aja.1001570109google scholar: lookup
            39. Nakagawa Y, Majima T, Nagashima K. Effect of ageing on ultrastructure of slow and fast skeletal muscle tendon in rabbit Achilles tendons.. Acta Physiol Scand 1994 Nov;152(3):307-13.
              pubmed: 7872008doi: 10.1111/j.1748-1716.1994.tb09810.xgoogle scholar: lookup
            40. Noble B. Bone microdamage and cell apoptosis.. Eur Cell Mater 2003 Dec 21;6:46-55; discusssion 55.
              pubmed: 14710370doi: 10.22203/ecm.v006a05google scholar: lookup
            41. Perez-Castro AV, Vogel KG. In situ expression of collagen and proteoglycan genes during development of fibrocartilage in bovine deep flexor tendon.. J Orthop Res 1999 Jan;17(1):139-48.
              pubmed: 10073658doi: 10.1002/jor.1100170120google scholar: lookup
            42. Ralphs JR, Benjamin M, Waggett AD, Russell DC, Messner K, Gao J. Regional differences in cell shape and gap junction expression in rat Achilles tendon: relation to fibrocartilage differentiation.. J Anat 1998 Aug;193 ( Pt 2)(Pt 2):215-22.
              pmc: PMC1467841pubmed: 9827637doi: 10.1046/j.1469-7580.1998.19320215.xgoogle scholar: lookup
            43. Segretain D, Falk MM. Regulation of connexin biosynthesis, assembly, gap junction formation, and removal.. Biochim Biophys Acta 2004 Mar 23;1662(1-2):3-21.
              pubmed: 15033576doi: 10.1016/j.bbamem.2004.01.007google scholar: lookup
            44. Sia MA, Woodward TL, Turner JD, Laird DW. Quiescent mammary epithelial cells have reduced connexin43 but maintain a high level of gap junction intercellular communication.. Dev Genet 1999;24(1-2):111-22.
              pubmed: 10079515doi: 10.1002/(sici)1520-6408(1999)24:1/2<111::aid-dvg11>3.0.co;2-pgoogle scholar: lookup
            45. Smith RK, Birch H, Patterson-Kane J, Firth EC, Williams L, Cherdchutham W, van Weeren WR, Goodship AE. Should equine athletes commence training during skeletal development?: changes in tendon matrix associated with development, ageing, function and exercise.. Equine Vet J Suppl 1999 Jul;(30):201-9.
              pubmed: 10659252doi: 10.1111/j.2042-3306.1999.tb05218.xgoogle scholar: lookup
            46. Smith RK, Birch HL, Goodman S, Heinegård D, Goodship AE. The influence of ageing and exercise on tendon growth and degeneration--hypotheses for the initiation and prevention of strain-induced tendinopathies.. Comp Biochem Physiol A Mol Integr Physiol 2002 Dec;133(4):1039-50.
              pubmed: 12485691doi: 10.1016/s1095-6433(02)00148-4google scholar: lookup
            47. Söhl G, Willecke K. Gap junctions and the connexin protein family.. Cardiovasc Res 2004 May 1;62(2):228-32.
              pubmed: 15094343doi: 10.1016/j.cardiores.2003.11.013google scholar: lookup
            48. Stephens PR, Nunamaker DM, Butterweck DM. Application of a Hall-effect transducer for measurement of tendon strains in horses.. Am J Vet Res 1989 Jul;50(7):1089-95.
              pubmed: 2774333
            49. Strocchi R, De Pasquale V, Guizzardi S, Govoni P, Facchini A, Raspanti M, Girolami M, Giannini S. Human Achilles tendon: morphological and morphometric variations as a function of age.. Foot Ankle 1991 Oct;12(2):100-4.
              pubmed: 1773989doi: 10.1177/107110079101200207google scholar: lookup
            50. Tsuzaki M, Yang X, Burt J. Avian tendon cells express multiple connexins but acute mechanical load reduces cell-cell coupling. Trans Orthop Res Soc Vol. 22. San Francisco: 1997. p. 712.
            51. Unger VM, Kumar NM, Gilula NB, Yeager M. Three-dimensional structure of a recombinant gap junction membrane channel.. Science 1999 Feb 19;283(5405):1176-80.
              pubmed: 10024245doi: 10.1126/science.283.5405.1176google scholar: lookup
            52. Waggett AD, Benjamin M, Ralphs JR. Connexin 32 and 43 gap junctions differentially modulate tenocyte response to cyclic mechanical load.. Eur J Cell Biol 2006 Nov;85(11):1145-54.
              pubmed: 16859807doi: 10.1016/j.ejcb.2006.06.002google scholar: lookup
            53. Webbon PM. A post mortem study of equine digital flexor tendons.. Equine Vet J 1977 Apr;9(2):61-7.
              pubmed: 862604doi: 10.1111/j.2042-3306.1977.tb03981.xgoogle scholar: lookup
            54. White TW, Paul DL, Goodenough DA, Bruzzone R. Functional analysis of selective interactions among rodent connexins.. Mol Biol Cell 1995 Apr;6(4):459-70.
              pmc: PMC301204pubmed: 7542941doi: 10.1091/mbc.6.4.459google scholar: lookup
            55. Williams RB, Harkins LS, Hammond CJ, Wood JL. Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.. Equine Vet J 2001 Sep;33(5):478-86.
              pubmed: 11558743doi: 10.2746/042516401776254808google scholar: lookup
            56. Wilson DA, Baker GJ, Pijanowski GJ, Boero MJ, Badertscher RR 2nd. Composition and morphologic features of the interosseous muscle in Standardbreds and Thoroughbreds.. Am J Vet Res 1991 Jan;52(1):133-9.
              pubmed: 2021241
            57. Yamaoka Y, Sawa Y, Ebata N, Ibuki N, Yoshida S. Cultured periodontal ligament fibroblasts express diverse connexins.. Tissue Cell 2002 Dec;34(6):375-80.
              pubmed: 12441089doi: 10.1016/s0040816602000381google scholar: lookup

            Citations

            This article has been cited 29 times.
            1. Peserico A, Barboni B, Russo V, Bernabò N, El Khatib M, Prencipe G, Cerveró-Varona A, Haidar-Montes AA, Faydaver M, Citeroni MR, Berardinelli P, Mauro A. Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling. Front Vet Sci 2023;10:1175346.
              doi: 10.3389/fvets.2023.1175346pubmed: 37180059google scholar: lookup
            2. Boyer KA, Hayes KL, Umberger BR, Adamczyk PG, Bean JF, Brach JS, Clark BC, Clark DJ, Ferrucci L, Finley J, Franz JR, Golightly YM, Hortobágyi T, Hunter S, Narici M, Nicklas B, Roberts T, Sawicki G, Simonsick E, Kent JA. Age-related changes in gait biomechanics and their impact on the metabolic cost of walking: Report from a National Institute on Aging workshop. Exp Gerontol 2023 Mar;173:112102.
              doi: 10.1016/j.exger.2023.112102pubmed: 36693530google scholar: lookup
            3. Korcari A, Nichols AEC, Buckley MR, Loiselle AE. Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype. Elife 2023 Jan 19;12.
              doi: 10.7554/eLife.84194pubmed: 36656751google scholar: lookup
            4. Macedo RS, Teodoro WR, Capellozzi VL, Rosemberg DL, Sposeto RB, de Cesar Netto C, Deland JT, Maffulli N, Ellis SJ, Godoy-Santos AL. Histoarchitecture of the fibrillary matrix of human fetal posterior tibial tendons. Sci Rep 2022 Oct 26;12(1):17922.
              doi: 10.1038/s41598-022-19695-3pubmed: 36289254google scholar: lookup
            5. 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
            6. Melzer M, Schubert S, Müller SF, Geyer J, Hagen A, Niebert S, Burk J. Rho/ROCK Inhibition Promotes TGF-β3-Induced Tenogenic Differentiation in Mesenchymal Stromal Cells. Stem Cells Int 2021;2021:8284690.
              doi: 10.1155/2021/8284690pubmed: 34659420google scholar: lookup
            7. Bianchi E, Ruggeri M, Rossi S, Vigani B, Miele D, Bonferoni MC, Sandri G, Ferrari F. Innovative Strategies in Tendon Tissue Engineering. Pharmaceutics 2021 Jan 11;13(1).
              doi: 10.3390/pharmaceutics13010089pubmed: 33440840google scholar: lookup
            8. Tsai SL, Nödl MT, Galloway JL. Bringing tendon biology to heel: Leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies. Dev Dyn 2021 Mar;250(3):393-413.
              doi: 10.1002/dvdy.269pubmed: 33169466google scholar: lookup
            9. Takahashi N, Kametani K, Ota R, Tangkawattana P, Iwasaki T, Hasegawa Y, Ueda H, Hosotani M, Watanabe T. Three-dimensional ultrastructure reconstruction of tendinous components at the bifurcation of the bovine superficial digital flexor tendon using array and STEM tomographies. J Anat 2021 Jan;238(1):63-72.
              doi: 10.1111/joa.13294pubmed: 32794178google scholar: lookup
            10. Hadate S, Takahashi N, Kametani K, Iwasaki T, Hasega Y, Tangkawattana P, Kawasaki T, Ueda H, Hosotani M, Watanabe T. Ultrastructural study of the three-dimensional tenocyte network in newly hatched chick Achilles tendons using serial block face-scanning electron microscopy. J Vet Med Sci 2020 Jul 31;82(7):948-954.
              doi: 10.1292/jvms.20-0120pubmed: 32418945google scholar: lookup
            11. Theodossiou SK, Murray JB, Schiele NR. Cell-cell junctions in developing and adult tendons. Tissue Barriers 2020;8(1):1695491.
              doi: 10.1080/21688370.2019.1695491pubmed: 31818195google scholar: lookup
            12. Fenu M, Bettermann T, Vogl C, Darwish-Miranda N, Schramel J, Jenner F, Ribitsch I. A novel magnet-based scratch method for standardisation of wound-healing assays. Sci Rep 2019 Sep 2;9(1):12625.
              doi: 10.1038/s41598-019-48930-7pubmed: 31477739google scholar: lookup
            13. 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
            14. Takahashi N, Tangkawattana P, Ootomo Y, Hirose T, Minaguchi J, Ueda H, Yamada M, Takehana K. Morphometric analysis of growing tenocytes in the superficial digital flexor tendon of piglets. J Vet Med Sci 2017 Dec 22;79(12):1960-1967.
              doi: 10.1292/jvms.17-0436pubmed: 29070765google scholar: lookup
            15. Barrett DW, David AL, Thrasivoulou C, Mata A, Becker DL, Engels AC, Deprest JA, Chowdhury TT. Connexin 43 is overexpressed in human fetal membrane defects after fetoscopic surgery. Prenat Diagn 2016 Oct;36(10):942-952.
              doi: 10.1002/pd.4917pubmed: 27568096google scholar: lookup
            16. Plotkin LI, Stains JP. Connexins and pannexins in the skeleton: gap junctions, hemichannels and more. Cell Mol Life Sci 2015 Aug;72(15):2853-67.
              doi: 10.1007/s00018-015-1963-6pubmed: 26091748google scholar: lookup
            17. Russo V, Mauro A, Martelli A, Di Giacinto O, Di Marcantonio L, Nardinocchi D, Berardinelli P, Barboni B. Cellular and molecular maturation in fetal and adult ovine calcaneal tendons. J Anat 2015 Feb;226(2):126-42.
              doi: 10.1111/joa.12269pubmed: 25546075google scholar: lookup
            18. Bayer ML, Schjerling P, Herchenhan A, Zeltz C, Heinemeier KM, Christensen L, Krogsgaard M, Gullberg D, Kjaer M. Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype. PLoS One 2014;9(1):e86078.
              doi: 10.1371/journal.pone.0086078pubmed: 24465881google scholar: lookup
            19. Schiele NR, Marturano JE, Kuo CK. Mechanical factors in embryonic tendon development: potential cues for stem cell tenogenesis. Curr Opin Biotechnol 2013 Oct;24(5):834-40.
              doi: 10.1016/j.copbio.2013.07.003pubmed: 23916867google scholar: lookup
            20. Agabalyan NA, Evans DJ, Stanley RL. Investigating tendon mineralisation in the avian hindlimb: a model for tendon ageing, injury and disease. J Anat 2013 Sep;223(3):262-77.
              doi: 10.1111/joa.12078pubmed: 23826786google scholar: lookup
            21. Hieda K, Hayashi S, Kim JH, Murakami G, Cho BH, Matsubara A. Spatial relationship between expression of cytokeratin-19 and that of connexin-43 in human fetal kidney. Anat Cell Biol 2013 Mar;46(1):32-8.
              doi: 10.5115/acb.2013.46.1.32pubmed: 23560234google scholar: lookup
            22. 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
            23. Barboni B, Curini V, Russo V, Mauro A, Di Giacinto O, Marchisio M, Alfonsi M, Mattioli M. Indirect co-culture with tendons or tenocytes can program amniotic epithelial cells towards stepwise tenogenic differentiation. PLoS One 2012;7(2):e30974.
              doi: 10.1371/journal.pone.0030974pubmed: 22348033google scholar: lookup
            24. Scutt N, Rolf CG, Scutt A. Tissue specific characteristics of cells isolated from human and rat tendons and ligaments. J Orthop Surg Res 2008 Jul 24;3:32.
              doi: 10.1186/1749-799X-3-32pubmed: 18652675google scholar: lookup
            25. DiStefano MS, Eekhoff JD, Weiss SN, Nuss CA, Betts RL, Kuntz AF, Soslowsky LJ. Murine Supraspinatus Tendons Demonstrate Aging-Related Changes in Multiscale Mechanics, Structure, and Gene Expression. J Orthop Res 2026 Jan;44(1):e70013.
              doi: 10.1002/jor.70013pubmed: 40575962google scholar: lookup
            26. Guillaumin S, Rossoni A, Zeugolis D. State-of the-art and future perspective in co-culture systems for tendon engineering. Biomater Biosyst 2025 Mar;17:100110.
              doi: 10.1016/j.bbiosy.2025.100110pubmed: 40130022google scholar: lookup
            27. Grinstein M, Tsai SL, Montoro D, Freedman BR, Dingwall HL, Villaseñor S, Zou K, Sade-Feldman M, Tanaka MJ, Mooney DJ, Capellini TD, Rajagopal J, Galloway JL. A latent Axin2(+)/Scx(+) progenitor pool is the central organizer of tendon healing. NPJ Regen Med 2024 Oct 17;9(1):30.
              doi: 10.1038/s41536-024-00370-2pubmed: 39420021google scholar: lookup
            28. Bakht SM, Pardo A, Gomez-Florit M, Caballero D, Kundu SC, Reis RL, Domingues RMA, Gomes ME. Human Tendon-on-Chip: Unveiling the Effect of Core Compartment-T Cell Spatiotemporal Crosstalk at the Onset of Tendon Inflammation. Adv Sci (Weinh) 2024 Nov;11(41):e2401170.
              doi: 10.1002/advs.202401170pubmed: 39258510google scholar: lookup
            29. Giduthuri AT, Theodossiou SK, Schiele NR, Srivastava SK. Dielectrophoresis as a tool for electrophysiological characterization of stem cells. Biophys Rev (Melville) 2020 Dec;1(1):011304.
              doi: 10.1063/5.0025056pubmed: 38505626google scholar: lookup
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