Human Tenocyte Differentiation Drives Adhesion Formation

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(4) For those patients who had scaled pain scores recorded in their charts,mean/median change in pain score was -4/-4 points (range -10 to þ2,n¼4) in PSB hands versus -2.64/-2 points (range -8 to þ2, n¼11) in PShands (P¼0.5529, WRST).

(5) Pre-operative arteriograms in hands that underwent PSB didnot accurately reflect the suitability of the radial or ulnar artery forbypass.

Summary Points:� Vascular bypass in conjunction with sympathectomy may be superior tosympathectomy alone in digital ischemia caused by collagen vasculardisease

� Suitability for vascular bypass should be determined intraoperatively byclinical assessment rather than by preoperative angiographic findings.

� If either the radial or ulnar artery is atretic or thrombosed, bypass shouldbe attempted.

� Royalties/Honoraria received from: Orthohelix Surgical Designs (Leversedge)� Consulting Fee: Stryker Orthopaedics, Axogen (Leversedge)� Contracted Research: Axogen, Bioventus (Leversedge)

PAPER 03

Best PapersThursday, September 18, 2014 � 2:29e2:34 PMCategory: Treatment, Prognosis/Outcomes, Basic ScienceKeyword: Hand and Wrist, Diseases and Disorders, General Principles

Human Tenocyte Differentiation Drives Adhesion FormationN/A - Not a clinical study

© Rowena McBeath, MD, PhD© A. Lee Osterman, MD

Hypothesis: The molecular and cellular signalling events responsible forhuman tendon adhesion formation are unclear. Prior in vitro studies ofhuman tenocytes have demonstrated tenocyte ‘dedifferentiation’ (1), as seenby change in shape (from elongated to round) and extracellular matrixproduction with growth in low-density culture. Correspondingly, we hy-pothesized that adhesion formation post-tendon injury and repair represents,in actuality, the tenocyte dedifferentiated state.Methods: Human tendon tissue was isolated from patients undergoingrevision amputation from traumatic hand injury as well as those undergoingdelayed tendon reconstruction using standard protocols (2). Tendon tissueand tenocytes underwent immunohistochemical and immunofluorescentstaining of collagen I, collagen II and aggrecan. Tenocytes were also har-vested for RT-PCR analysis of tenocyte markers tenomodulin, scleraxis,collagen I; and fibrochondrocyte markers collagen II and aggrecan.Biochemical assays for RhoA GTPase activity are as described (3). Acti-vation of RhoA GTPase using adenoviral transduction is as described (4).Results: Normal human tenocytes are elongated and produce predominantlycollagen I. Tenocytes harvested from tendon that has adhered to sur-rounding tissue (‘adherent tenocytes’) display increased stress fiber for-mation, and produce more aggrecan than normal tenocytes. When analyzedfor biochemical activity, adherent tenocytes express higher active RhoAGTPase levels than their normal counterparts. Furthermore, activation ofRhoA GTPase in normal human tenocytes reproduces the adherent tenocytecellular and molecular phenotype, in the form of rounded cell shape andincreased aggrecan production.Summary Points:� While ordinarily thought to be due to a balance of intrinsic and extrinsicforces, we hypothesize that tendon adhesion formation post-injury actu-ally represents a novel tenocyte differentiation state.

� Adherent tenocytes have increased stress fiber formation, express higherlevels of aggrecan, and display a rounded cell morphology in tissue.

� Biochemical analysis reveals high RhoA activity levels in the adherenttenocyte differentiated state.

� Activation of RhoA GTPase in normal human tenocytes reproduces theadherent tenocyte phenotype.

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� These results suggest that tendon adhesion formation is due to changes intenocyte differentiation, and suggest a molecular mechanism by whichthis occurs.

� Clinical implications of these results affect tendon repair, tendon healing,adhesion formation and tendon regeneration.

REFERENCES

1. Yao L, Bestwick CS, Bestwick LA, Maffulli N, Aspden RM. Phenotypic drift inhuman tenocyte culture. Tissue Eng. 2006;12(7):1843e1849.

2. Qiu Y, Wang X, Zhang Y, et al. In vitro two-dimensional and three-dimensionaltenocyte culture for tendon tissue engineering. J Tissue Eng Regen Med. 2013.Aug. 29 [Epub ahead of print].

3. Ren XD, Schwartz MA. Determination of GTP loading on Rho. Methods Enzymol.2000;325:264e272.

4. Pattabiraman PP, Rao PV. Mechanistic basis of Rho GTPase-induced extracel-lular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol.2010;298(3):C749eC763.

PAPER 04

Best PapersThursday, September 18, 2014 � 2:34e2:39 PMCategory: Treatment, Prognosis/Outcomes, AnatomyKeyword: Elbow and Forearm, Congenital and Pediatric Problems, Nerve

Recovery of Motor Nerve Injuries Associated With Displaced,Extension-Type Pediatric Supracondylar Humerus FracturesLevel 4 Evidence

© Bryce T. Gillespie, MD© Benjamin J. Shore, MD, MPH© Patricia E. Miller, MS© Donald S. Bae, MD© Peter M. Waters, MD

Hypothesis: Nerve injuries occur in approximately 13% of pediatric exten-sion-type supracondylar humerus fractures, but no large-scale studies haveanalyzed recovery of these nerve injuries (Ref 1). We hypothesized that thetime to recovery for a motor nerve palsy associated with a supracondylarhumerus fracture would vary by which nerve is injured, if more than onenerve is injured, and if immediate decompression of the affected nerve(s)occurred at the time of fracture fixation.Methods: Two hundred and seventeen children with traumatic nerve injuriesassociated with displaced, extension-type pediatric supracondylar humerusfractures treated at a single institution between 1996 and 2012 werereviewed. Fractures were treated with closed or open reduction and percu-taneous pinning. We distinctly identified those patients who had decom-pression of the affected nerve(s) at the time of fracture fixation. Nerve injurieswere excluded if: iatrogenic, paresthesia only without motor deficit, asso-ciated with flexion-type or intra-articular distal humerus fractures. Multi-variable general linear modeling using a lognormal transformation of time torecovery was used to compare recovery times across nerve injury types andto determine the effect of injury and treatment characteristics on recoverytime.Results: Subjects had a mean age of 6.4 years and 139 (65%) sustained anisolated median nerve injury (inclusive of anterior interosseous nerve-onlyinjuries) (Tables 1 and 2). Sixty-three (24%) patients had concurrentvascular injuries ranging from weak pulse to brachial artery transection.

Forty patients had immediate nerve decompression at the time offracture fixation. Three patients required later surgical intervention for poornerve recovery (two had median nerve neurolysis and one had tendontransfers for radial nerve palsy); none of these three had undergone nervedecompression at the time of fracture fixation.

172 patients had recovery of the nerve injury by final follow-up. Most(53%) recovered within 3 months from injury and the overall mean time torecovery was 2.8 months (SD 2.2).Summary Points:� If either the radial or ulnar artery is atretic or thrombosed, bypass shouldbe attempted.

© Speaker has nothing of financial value to disclose

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