Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 7/2013

01-07-2013 | Experimental Study

Detection of slow-cycling and stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise

Authors: Eva Runesson, Paul Ackermann, Helena Brisby, Jón Karlsson, Bengt I. Eriksson

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 7/2013

Login to get access

Abstract

Purpose

Tendons generally exhibit poor healing capacity, probably due to slow cell regeneration potential and low vascularization. The potential to regenerate may partly be due to activation of stem/progenitor cells localized in the tendon or its vicinity. In the present study, we attempted to determine where in the rat Achilles tendon stem/progenitor cells reside and to investigate the effect of exercise on cell proliferation in the in vivo situation.

Method

We used bromodeoxyuridine (BrdU) labelling to investigate proliferation and label-retaining cells (i.e. slow-cycling cells) in non-exercised and exercised rats, in combination with immunostaining of the stem cell marker nucleostemin. Rat Achilles tendons were harvested 14, 28, 56 and 105 days after BrdU administration.

Results

We found the proportion of stem/progenitor cells to be twice as high in the distal tendon (DT) compared with the mid/proximal tendon (MPT) and that paratenon/endotenon regions appear to host a pool of existing stem/progenitor cells. Exercise increased the BrdU-stained cell population after 14 days only (DT region p = 0.032, MPT p = 0.065), indicating effect mainly on more differentiated cells, since the nucleostemin-positive cells (i.e. stem/progenitor cells) remained unaffected in the intact Achilles tendon.

Conclusion

Stem/progenitor cells exist in several areas of the rat Achilles tendon which implies a possible stem cell regeneration pool of different origins. The distal region has twice the amount of stem/progenitor cells compared with the mid/proximal region, indicating a potentially higher stem cell activity in this tissue. Daily moderate exercise (treadmill running) mainly improves in vivo cell proliferation in rapidly proliferating cells, whereas the stem/progenitor pool remains constant.
Literature
1.
go back to reference Ackermann PW, Salo PT, Hart DA (2009) Neuronal pathways in tendon healing. Front Biosci 14:5165–5187PubMedCrossRef Ackermann PW, Salo PT, Hart DA (2009) Neuronal pathways in tendon healing. Front Biosci 14:5165–5187PubMedCrossRef
2.
go back to reference Benjamin M, Evans EJ, Copp L (1986) The histology of tendon attachments to bone in man. J Anat 149:89–100PubMed Benjamin M, Evans EJ, Copp L (1986) The histology of tendon attachments to bone in man. J Anat 149:89–100PubMed
3.
go back to reference Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of extracellular matrix in their niche. Nat Med 13:1219–1227PubMedCrossRef Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of extracellular matrix in their niche. Nat Med 13:1219–1227PubMedCrossRef
4.
go back to reference Boushel R, Langberg H, Green S, Skovgaard D, Bulow J, Kjaer M (2000) Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans. J Physiol 524:305–313PubMedCrossRef Boushel R, Langberg H, Green S, Skovgaard D, Bulow J, Kjaer M (2000) Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans. J Physiol 524:305–313PubMedCrossRef
5.
go back to reference Couppé C, Kongsgaard M, Aagaard P, Hansen P, Bojsen-Moller J, Kjaer M, Magnusson SP (2008) Habitual loading results in tendon hypertrophy and increased stiffness of the human patellar tendon. J Appl Physiol 105:805–810PubMedCrossRef Couppé C, Kongsgaard M, Aagaard P, Hansen P, Bojsen-Moller J, Kjaer M, Magnusson SP (2008) Habitual loading results in tendon hypertrophy and increased stiffness of the human patellar tendon. J Appl Physiol 105:805–810PubMedCrossRef
6.
go back to reference Gineyts E, Cloos PA, Borel O, Grimaud L, Delmas PD, Garnero P (2000) Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissue: assessment of tissue turnover. Biochem J 345:481–485PubMedCrossRef Gineyts E, Cloos PA, Borel O, Grimaud L, Delmas PD, Garnero P (2000) Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissue: assessment of tissue turnover. Biochem J 345:481–485PubMedCrossRef
7.
go back to reference Glazebrook MA, Wright JR, Langman M, Stanish WD, Lee JM (2008) Histological analysis of achilles tendons in an overuse rat model. J Orthop Res 26:840–846PubMedCrossRef Glazebrook MA, Wright JR, Langman M, Stanish WD, Lee JM (2008) Histological analysis of achilles tendons in an overuse rat model. J Orthop Res 26:840–846PubMedCrossRef
8.
go back to reference Heinemeier KM, Olesen JL, Haddad F, Langberg H, Kjaer M, Baldwin KM, Schjerling P (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582:1303–1316PubMedCrossRef Heinemeier KM, Olesen JL, Haddad F, Langberg H, Kjaer M, Baldwin KM, Schjerling P (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582:1303–1316PubMedCrossRef
9.
go back to reference Henriksson H, Thornemo M, Karlsson C, Hägg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34:2278–2287CrossRef Henriksson H, Thornemo M, Karlsson C, Hägg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34:2278–2287CrossRef
10.
go back to reference Holm L, Reitelseder S, Pedersen TG, Doessing S, Petersen SG, Flyvbjerg A, Andersen JL, Aagaard P, Kjaer M (2008) Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity. J Appl Physiol 105:1454–1461PubMedCrossRef Holm L, Reitelseder S, Pedersen TG, Doessing S, Petersen SG, Flyvbjerg A, Andersen JL, Aagaard P, Kjaer M (2008) Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity. J Appl Physiol 105:1454–1461PubMedCrossRef
11.
go back to reference Hong HS, Lee J, Lee E, Kwon YS, Lee E, Ahn W, Jiang MH, Kim JC, Son Y (2009) A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nat Med 15:425–435PubMedCrossRef Hong HS, Lee J, Lee E, Kwon YS, Lee E, Ahn W, Jiang MH, Kim JC, Son Y (2009) A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nat Med 15:425–435PubMedCrossRef
12.
go back to reference Karlsson C, Thornemo M, Henriksson HB, Lindahl A (2009) Identification of a stem cell niche in the zone of Ranvier within the knee joint. J Anat 215:355–363PubMedCrossRef Karlsson C, Thornemo M, Henriksson HB, Lindahl A (2009) Identification of a stem cell niche in the zone of Ranvier within the knee joint. J Anat 215:355–363PubMedCrossRef
13.
go back to reference Kim SJ, Cheung S, Hellerstein MK (2004) Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon. Am J Physiol Cell Physiol 286:C1464–C1473PubMedCrossRef Kim SJ, Cheung S, Hellerstein MK (2004) Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon. Am J Physiol Cell Physiol 286:C1464–C1473PubMedCrossRef
14.
go back to reference Ksiezopolska-Orlowska K (2010) Changes in bone mechanical strength in response to physical therapy. Pol Arch Med Wewn 120:368–373PubMed Ksiezopolska-Orlowska K (2010) Changes in bone mechanical strength in response to physical therapy. Pol Arch Med Wewn 120:368–373PubMed
15.
go back to reference Maffulli N, Longo U, Sharma P, Denaro V (2010) Tendon injury and repair mechanics. In: Archer C, Ralphs J (eds) Regenerative medicine and biomaterials for the repair of connective tissue. Woodhead Publishing Limited, Cambridge, pp 394–418CrossRef Maffulli N, Longo U, Sharma P, Denaro V (2010) Tendon injury and repair mechanics. In: Archer C, Ralphs J (eds) Regenerative medicine and biomaterials for the repair of connective tissue. Woodhead Publishing Limited, Cambridge, pp 394–418CrossRef
16.
go back to reference Magnusson SP, Langberg H, Kjaer M (2010) The pathogenesis of tendinopathy: balancing the response to loading. Nat Rev Rheumatol 6:262–268PubMedCrossRef Magnusson SP, Langberg H, Kjaer M (2010) The pathogenesis of tendinopathy: balancing the response to loading. Nat Rev Rheumatol 6:262–268PubMedCrossRef
17.
go back to reference Orford KW, Scadden DT (2008) Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat Rev Genet 2:115–128CrossRef Orford KW, Scadden DT (2008) Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat Rev Genet 2:115–128CrossRef
19.
go back to reference Sasaki N, Henriksson HB, Runesson E, Larsson K, Sekiguchi M, Kikuchi S, Konno S, Rydevik B, Brisby H (2012) Physical exercise affects cell proliferation in lumbar intervertebral disc regions in rats. Spine (Phila Pa 1976) 37:1440–1447CrossRef Sasaki N, Henriksson HB, Runesson E, Larsson K, Sekiguchi M, Kikuchi S, Konno S, Rydevik B, Brisby H (2012) Physical exercise affects cell proliferation in lumbar intervertebral disc regions in rats. Spine (Phila Pa 1976) 37:1440–1447CrossRef
20.
go back to reference Skovgaard D, Bayer ML, Mackey AL, Madsen J, Kjaer M, Kjaer A (2010) Increased cellular proliferation in rat skeletal muscle and tendon in response to exercise: use of FLT and PET/CT. Mol Imaging Biol 12:626–634PubMedCrossRef Skovgaard D, Bayer ML, Mackey AL, Madsen J, Kjaer M, Kjaer A (2010) Increased cellular proliferation in rat skeletal muscle and tendon in response to exercise: use of FLT and PET/CT. Mol Imaging Biol 12:626–634PubMedCrossRef
21.
go back to reference Szczodry M, Zhang J, Lim C, Davitt HL, Yeager T, Fu FH, Wang JH (2009) Tredmill running exercise results in the presence of numerous myofibroblasts in mouse patellar tendon. J Orthop Res 27:1373–1378PubMedCrossRef Szczodry M, Zhang J, Lim C, Davitt HL, Yeager T, Fu FH, Wang JH (2009) Tredmill running exercise results in the presence of numerous myofibroblasts in mouse patellar tendon. J Orthop Res 27:1373–1378PubMedCrossRef
22.
go back to reference Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461PubMedCrossRef Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461PubMedCrossRef
23.
go back to reference Tempfer H, Wagner A, Gehwolf R, Lehner C, Tauber M, Resch H, Bauer HC (2009) Perivascular cells of the supraspinatus tendon express both tendon- and stem cell-related markers. Histochem Cell Biol 131:733–741PubMedCrossRef Tempfer H, Wagner A, Gehwolf R, Lehner C, Tauber M, Resch H, Bauer HC (2009) Perivascular cells of the supraspinatus tendon express both tendon- and stem cell-related markers. Histochem Cell Biol 131:733–741PubMedCrossRef
24.
go back to reference Tsai RY, McKay RD (2002) A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev 16:2991–3003PubMedCrossRef Tsai RY, McKay RD (2002) A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev 16:2991–3003PubMedCrossRef
25.
go back to reference Yang G, Crawford RC, Wang JH (2004) Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech 37:1543–1550PubMedCrossRef Yang G, Crawford RC, Wang JH (2004) Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech 37:1543–1550PubMedCrossRef
26.
go back to reference Zeichen J, van Griensven M, Bosch U (2000) The proliferative response of isolated human tendon fibroblasts to cyclic biaxial mechanical strain. Am J Sports Med 28:888–892PubMed Zeichen J, van Griensven M, Bosch U (2000) The proliferative response of isolated human tendon fibroblasts to cyclic biaxial mechanical strain. Am J Sports Med 28:888–892PubMed
27.
go back to reference Zhang J, Pan T, Im HJ, Fu FH, Wang JH (2011) Differential properties of human ACL and MCL stem cells may be responsible for their differential healing capacity. BMC Med 9:68PubMedCrossRef Zhang J, Pan T, Im HJ, Fu FH, Wang JH (2011) Differential properties of human ACL and MCL stem cells may be responsible for their differential healing capacity. BMC Med 9:68PubMedCrossRef
28.
go back to reference Zhang J, Pan T, Liu Y, Wang JH (2010) Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC-related cellular production of collagen. J Orthop Res 28:1178–1183PubMedCrossRef Zhang J, Pan T, Liu Y, Wang JH (2010) Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC-related cellular production of collagen. J Orthop Res 28:1178–1183PubMedCrossRef
29.
go back to reference Zhang J, Wang JH (2010) Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. J Orthop Res 28:639–643PubMedCrossRef Zhang J, Wang JH (2010) Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. J Orthop Res 28:639–643PubMedCrossRef
30.
go back to reference Zhang J, Wang JH (2010) Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord 11:10PubMedCrossRef Zhang J, Wang JH (2010) Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord 11:10PubMedCrossRef
Metadata
Title
Detection of slow-cycling and stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise
Authors
Eva Runesson
Paul Ackermann
Helena Brisby
Jón Karlsson
Bengt I. Eriksson
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 7/2013
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-013-2446-7

Other articles of this Issue 7/2013

Knee Surgery, Sports Traumatology, Arthroscopy 7/2013 Go to the issue