tendon homeostasis, tendinopathy and healing · tendon homeostasis, tendinopathy and healing alayna...
TRANSCRIPT
![Page 1: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/1.jpg)
Tendon Homeostasis, Tendinopathy and Healing
Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course
April 17th, 2017
![Page 2: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/2.jpg)
Outline
• Overviewoftendonstructure/func1on• EffectsofAging• Disrup1onsinhomeostasis• Pathogenesisoftendinopathy/tendini1s• Mechanismsofregenera1onandhealing
JOR:NewFron1ersinTendonResearchJune2015
7ReviewAr1cles15PrimaryResearchPapers
![Page 3: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/3.jpg)
TendonStructure&Func1on
Nourissat, G. et al. (2015) Tendon injury: from biology to tendon repair Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2015.26
• Transmissionofforcesfrommuscletobone
• Movementofnearlytheen1reskeleton
• Crimpstructureincreaseselas1city
• Hierarchicalnatureallowsforceconduc1ondispropor1onatetosize
![Page 4: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/4.jpg)
3AB'2(0E(3'&40&(
•! ;(-%1(+:>'"-E'#+#$5<'-*($%+5'
•! F+*$:-<+("%:>'"-E'#G*$:-<+("%:>'
![Page 5: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/5.jpg)
F5&G5/002(2#0/'(<9H(4"/%&G(I"@B%&G((F5&G5/00(>3J2(5/'(@"67(($0&G'/(#75&(7"@5&(
K"@5&2(2#0/'(89H(4"/%&G(/"&&%&G(
L&'/GA(C#0/%&G(?0#'&15$(
H.($:E/(9'
![Page 6: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/6.jpg)
>&%@5$(M04'$2(0E(3'&4%&0B5#7A(D(K'5$%&G(C"B/52B%&5#"2(N/0#5#0/(6"OP(((((((>67%$$'2(3'&40&((((((((?5#'$$5/(3'&40&((((((((((.$'Q0/(3'&40&(
M0"2'(R5&%&'(R7%6S'&(*5#(*5TT%#(K0/2'(?%G(
M0"2'(*5#(*5TT%#(
M0"2'(*5#(
!='/(U9(5&%@5$2(675/56#'/%V'4:(((
@02#(60@@0&+(*5#(
M0"2'(
N:P! C02$0-2SA(W)X('#(5$YX()(C70"$4'/(L$T0-(C"/G(:ZZ[\;+U]U^UZ8(N8P! 370@0B0"$02('#(5$YX()!*Y(89:;(N/'=%'-P(
M'675&%65$(((67'@%65$((
R0@B$'#'(#/5&2'610&((_`a(/'B5%/(
?5/15$(#/5&2'610&(b%0B2A(B"&67(
3'&4%&0B5#7A(
K'5$%&G(
C"B/52B%&5#"2(N/0#5#0/(6"OP(((((((>67%$$'2(3'&40&((((((((?5#'$$5/(3'&40&((((((((((.$'Q0/(3'&40&(
b%0B2A(B"&67(R0@B$'#'(#/5&2'610&(
(_(/'B5%/(?5/15$(#/5&2'610&(b%0B2A(B"&67(
M'675&%65$( .51G"'($054%&G(
."$$(#7%6S&'22X(B5/15$(-%4#7(3'&40&(#0(T0&'(7'5$%&G(
![Page 7: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/7.jpg)
c'T/5d27e(
JW Chen and JL Galloway. Methods in Cell Biology, Volume 138, 2017, 299–320
IJKL'!MN':@-*$:/*')$(9'O:>>(&:<'P:@'
![Page 8: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/8.jpg)
Pulleys Sheath
FDS
FDL
FDS
FDL
Mouse
Human
Wongetal.2006.J.Anatomy
Compara1veAnatomy
Hastetal.,2014Bone&Joint
![Page 9: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/9.jpg)
TendonHomeostasisYoung Aged
• Matrixcomposi1onandorganiza1onisnotdrama1callydifferent• Decreasedproteoglycancontent• Changesincellmorphology
Func1onalConsequencesofAging?
![Page 10: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/10.jpg)
Tendonisnotmechanicallysensi1vetoaging
Ackermanetal.,2017.JOR
TTFascicle
FDL
FCU
![Page 11: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/11.jpg)
3'&40&(D(>G%&G(•! 3'&06A#'(f"%'26'&6'(5&4($0-aE/'f"'&6A(LRM(#"/&0='/h(4'6/'52'4(2'&2%1=%#A(#0(5G%&G(N=2Y(T0&'P(
•! K0-'='/X(5G%&G(%2(52206%5#'4(-%#7+(%&6/'52'4(#'&4%&0B5#7AX(%@B5%/'4(7'5$%&G(
•! iB0&(675$$'&G'(N%&I"/AX(60@0/T%4%1'2P(5G'4(#'&06A#'2(75='(%@B5%/'4(5T%$%#A(#0(/'2B0&4(/'2"$1&G(%&(5G'a/'$5#'4(#'&40&(B5#70$0GA(
![Page 12: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/12.jpg)
3'&4%&0B5#7A(6%-#:-#'()'*8#'*#+,(+'
•! ;:%+).>'•! 2G:/#$@:*#,'@<':/1"%*<'•! =(-*'/(99(+'%+'*8#'4/8%>>#-'•! ?#+,(+%1-[':/.*#'%+\:99:1(+':+,'%+].$<'[':/.*#'%+\:99:1(+':+,'%+].$<'
N/%"#*E/(9'
![Page 13: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/13.jpg)
3'&4%&0B5#7A(6%-#:-#'()'*8#'*#+,(+'
•! ;:%+).>'•! 2G:/#$@:*#,'@<':/1"%*<'
•! ?#+,%+(-%-['/8$(+%/'&%*8',#5#+#$:1"#'/#>>.>:$'/8:+5#-U'+('%+\:99:1(+'
•! =($#'/(99(+'*8:+'*#+,%+%1-'•! B(+1+.%+5')($'>(+5#$'*8:+'S'9(+*8-'
N/%"#*E/(9'
['/8$(+%/'&%*8',#5#+#$:1"#'/#>>.>:$'
B(+1+.%+5')($'>(+5#$'*8:+'S'9(+*8-'
![Page 14: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/14.jpg)
3'&02A&0=%12(•! F+\:99:1(+'()'*8#'-8#:*8'•! B:.-#-['%+\:99:*($<',%-#:-#-U'%+)#/1(+U'
%+].$<'•! =(-*'/(99(+><'%+'8:+,0'&$%-*'
N/%"#*E/(9'
![Page 15: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/15.jpg)
TendonRupture
SRRaikin.LowerextremityReview.2014
Achillesismostsuscep1ble
Sex-baseddifferences
![Page 16: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/16.jpg)
j%2/"B#'4(K0@'02#52%2+(K0/@0&5$(LO'6#2(
•! 2-*$(5#+'M#/#7*($-':$#'#G7$#--#,'@<'*#+(/<*#-K'
•! !^_['-#+-%1"%*<'":$%#-'@<'*#+,(+`'•! ;$#a9#+(7:.-:>'&(9#+'8:"#',#/$#:-#,'$%-A'
()'*#+,%+(7:*8<'$#>:1"#'*('9#+E'';(-*a9#+(7:.-#['#b.%":>#+*'$%-AK'
•! CM?['%97$("#-'*#+,(+'-*$./*.$#'%+':/1"#'@.*'+(*'-#,#+*:$<'7:1#+*-I'
K'M#"%#&#,'%+'Q$%DD%#$('4'#*':>E'=P?T'IJKVU'IB((A'TP'#*':>E'N/:+,'T'()'=#,'X'N/%'%+'N7($*-E'IJJS'
![Page 17: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/17.jpg)
j%2/"B#'4(K0@'02#52%2+(j%5T'#'2(
R0&#/0$( j%5T'16(
•! N#+-%1"%*<'":$%#-'@<'*#+,(+`'•! Q>#G($-':$#'9(-*'-#+-%1"#'•! ;:*8(>(5%/:>'/8:+5#-'%+/$#:-#'&%*8',%-#:-#'
,.$:1(+'•! ?<7#'F':+,'*<7#'FF',%:@#1/-':$#'#b.:>><'-.-/#71@>#'
*('\#G($'*#+,%+(7:*8<'•! F+/$#:-#,'$:*#'()'$.7*.$#'•! ?I6=').$*8#$'%97:%$-'*#+,(+'8#:>%+5':c#$'
$.7*.$#'($'%+].$<'
![Page 18: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/18.jpg)
CollagenaseInducedTendinopathy
LD=lowdoseHD=highdosecollagenase
Inducesdegenera1vechangesviacollagendegrada1on
OrfeiCetal.(2016)PLOSONE11(8):e0161590.
![Page 19: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/19.jpg)
MechanicallyInducedTendinopathy• Fa1gueloadedunderanaesthesia• Uphilltreadmillrunning• Downhilltreadmillrunning
NeviaserA.2012.JShoulderElbowSurg. NAndarawis-Purietal.,2014.JOR
UnloadedLowlevelloading
Moderateloading
Highlevelloading
Fa1gueLoadingInducesApoptosis
Inducesmatrixandcellularchanges
![Page 20: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/20.jpg)
SummaryofTendinopathy
FutureDirec1ons• Con1nuetoiden1fyco-morbidi1esthatpredisposeoracceleratetendinopathy• Mostclinicaldataarefromlatestagepathology
• Beginningtousegene1canimalsmodelstobelerunderstandtendinopathy
RemodelingBalancePhysiologicalexerciseincreases:prolifera1on
collagenproduc1on tenocy1cgeneexpression(w/ochondro/osteo/adipo)
Overuse/Fa1gue:MatrixDamageTenocyteapoptosis
EffectsofPathologyand/orco-morbidi1es:promotedegenera1on+/-inflamma1on
Smokingobesityhighcholesterol
![Page 21: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/21.jpg)
3'&40&(K'5$%&G(•! ((nU99X999(#'&40&(/'B5%/(B/06'4"/'2(B'/(A'5/(
•! ((!='/(o89(b%$$%0&(%&(52206%5#'4(7'5$#7(65/'(602#2(
•! ((K'5$%&G(%2(60@B$%65#'4(TA(265/(E0/@510&(
,0/@5$(#'&40&( C65/(3%22"'(
,#'T(+5'IJKVk';#++%-%'IJJIk'W#$#,]%A>%:+'IJJlk'6#)$:+/('IJJV'''''
![Page 22: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/22.jpg)
Complica1onsofFlexorTendonHealing
CentersforDiseaseControlandPrevention.(2015,January).Strickland,J.W.etal.,JHandSurg[Am]25(2):p.214-235,(2000).Aydin,A.etal.,AOTT28(1):p.54-9,(2004).
Palmarsurfaceofhand
Tendon
Adhesion
Medscape.com
Ø Flexorandextensortendonsofthehandarethemostcommonlyinjuredtendons
Ø Fibro1cHealing:ExuberantECMdeposi1onalachestendontosynovialsheathandsurrounding1ssues
Ø HealingofflexortendonsiscomplicatedbyROM-limi1ngscarinupto40%ofrepairs
Ø Oqenrequireasecondarysurgicalproceduretolyseadhesions
Adhesion
![Page 23: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/23.jpg)
>6f"%2%10&(0E(M'675&%65$(?/0B'/1'2(
Maximum Load at Failure
14 21 28 35 42 49 63 0
2
4
6
8
10
Days Post-Surgery
[N]
Control
.$'Q0/(3'&40&(
P(%-#>>#'#*':>EU'IJJjE'T!M' ;'2>%:--(+'#*':>EU'IJJjE'T'477>';8<-E''
.+>(:,#,' >(:,#,'
>67%$$'2(3'&40&(
![Page 24: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/24.jpg)
Similari1esbetweenwoundandtendonhealing
AJJomasetal.2014.AdvancedDrugDeliveryReview
Thiruvothetal.2015.Plas1candAesthe1cResearch
![Page 25: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/25.jpg)
Inflamma1on
• Beginsimmediatelyacerinjury,lastsfor~1week
![Page 26: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/26.jpg)
Well-regulatedinflamma1onisbeneficial-ac1vateshealingcascade
-recruitment/ac1va1onofcellsExcessive/Chronicinflamma1onispathological
-degenera1vematrixchanges-fibro1chealing
Inflamma1on
BenefitsofAn1-inflammatorytherapyiscontroversialTimingmaybekey!
Generallyeffec1veatpreven1ngexcessscarforma1onEarlyinhibi1ondecreasesmechanicsDelayedhealingmaintainsmechanics
Cell-typespecificconsidera1ons
Virchenkoetal.,2004.AmJSportsMed,Gearyetal.2015.PlosOne
![Page 27: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/27.jpg)
Prolifera1ve/Granula1onPhase• Lastsafewweeks• Begins~day7inmousemodel• Prolifera1onof‘fibroblasts’• Bridgingoninjurysite• Produc1onofECMcomponents(Col1/Col3)• Rapiddeposi1onofdisorganizedECM
Day3 Day14PDGFandbFGF:promoteprolifera1on-canalsocauseadhesionsTGFB:Smad3-/-,PAI-1-/-reducesadhesionsS100a4:Abla1onreducesadhesionforma1on
Thomopoulosetal.,2009.JOR,Thomopoulosetal.,2010.JBJS,Katzeletal.2010.JOR,AwadLab,LoiselleLab
![Page 28: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/28.jpg)
RemodelingPhase• Lastsmanymonths• Begins~day21inmousemodel• Reorienta1onofECM• Mmp-mediatedremodeling
Day21
![Page 29: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/29.jpg)
CellularBasisofHealing
• Time-dependentdynamiccellularenvironment• Involvesmul1plecelltypes• Tenocyteapoptosis• Extrinsicinflammatorycells• Residenttenocytes,epitenoncells,sheathcells,tendonbasementmembranecells
• Bonemarrowderivedcells
![Page 30: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/30.jpg)
R'$$"$5/(b52%2(0E(K'5$%&G+(k&#/%&2%6(R'$$2(3'&06A#'2+(C6Q(/'@5%&2(T'2#(@5/S'/(-%#7(G'&'16(#00$2(
C(&#>>'#*':>EU'IJKLE'N/%M#7'
![Page 31: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/31.jpg)
6<9#+*'#*':>EU'IJKVE';>(-!+#'
C6Q(CM>(
R0&#/%T"10&(0E(C6$'/5Q%2(R'$$2(#0(K'5$%&GX((*'G'&'/510&(5&4(C65/(.0/@510&(%2(i&6$'5/(
."&610&(%2($%S'$A(#0(T'(60&#'Q#(4'B'&4'&#(
![Page 32: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/32.jpg)
R'$$"$5/(b52%2(0E(K'5$%&G+(k&#/%&2%6(R'$$2(
?:<>($'#*':>EU'IJKKE';>(-!+#'
W5@%&%&(
R0&#/%T"10&(0E(T52'@'&#(@'@T/5&'(N$5@%&%&_P(6'$$2(#0(7'5$%&G(5&4(547'2%0&(E0/@510&(
![Page 33: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/33.jpg)
R'$$"$5/(b52%2(0E(K'5$%&G+(LQ#/%&2%6(R'$$2(
j5A(8:(
?#+,(+'
?#+,(+'
N/:$'?%--.#'
R0&#/0$(
?#+,(+'
b0&'(M5//0-(j'/%='4(R'$$2(M%G/5#'(CB'6%d65$$A(#0(#7'(*'B5%/(C%#'(
P(%-#>>#'#*':>EU'IJKIE';>(-!+#U'q:]%A:&:U'YE'#*':>E'T(.$+:>'()'B#>>';8<-%(>(5<E'IJJL'
i&a%&I"/'4( j5A(U(
•! N7#/%n/'N.@a7(7.>:1(+-'$#9:%+'.+A+(&+'
•! Q.+/1(+'+(*'m/>#:$''•! W=a=97j'-.r/%#+*')($'
:,8#-%(+')($9:1(+'
![Page 34: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/34.jpg)
*'G'&'/51='(K'5$%&G+(L@T/A0&%6(
W#$#,]%A>%:+';q'#*':>EU'IJJlE'4++:>-'()'W%(9#,%/:>'2+5%+##$%+5'
Q#*:>[''P(&'>#"#>-'()'?OQWK'
:+,'?OQWI'C%58'>#"#>-'()'?OQWl'
.'#5$(C7''B( M5#"/'(C7''B(
i&a%&I"/'4(
i&a%&I"/'4(
k&I"/'4(
k&I"/'4(
![Page 35: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/35.jpg)
*'G'&'/51='(K'5$%&G+(L@T/A0&%6(
W#$#,]%A>%:+';q'#*':>EU'IJJSE'T!M'
![Page 36: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/36.jpg)
*'G'&'/51='(K'5$%&G+(,'0&5#5$(
C(&#>>'#*':>EU'IJKL'N/%M#7'
![Page 37: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/37.jpg)
N/8&:$*D'4O'#*':>EU'IJKLU'6#"#>(79#+*'
*'G'&'/51='(K'5$%&G+(,'0&5#5$(3/56%&G(s$%:a$%&'5G'(6'$$2(5q'/(''2%2(%&I"/A(
s$%_(g#(+:*:>' Y(.+5':,.>*'
![Page 38: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/38.jpg)
Wheredowegofromhere?
• Cri1calmassoflabsstudyingcelllineage/fate/func1on
• Developmentoftendonspecifictools• Bigdataandsingle-cellRNAseq• Iden1fica1onofnew‘tendon-specific’markers
![Page 39: Tendon Homeostasis, Tendinopathy and Healing · Tendon Homeostasis, Tendinopathy and Healing Alayna E. Loiselle, PhD CMSR T32 Musculoskeletal Basic Science Course April 17th, 2017](https://reader030.vdocument.in/reader030/viewer/2022021802/5b78280c7f8b9a47518e99ca/html5/thumbnails/39.jpg)
''
W#$#,]%A>%:+'IJJlE'TWTN' W:8+#<'#*':>EU'IJKiE'Q$(+*'2+,(/$%+(>E''