Cadaver canine shoulder (right) with skin and periscapular muscles removed.

<p>(A) Posterior bursal view: The supraspinatus (yellow), infraspinatus (pink) and teres minor muscles (blue) can be visualized. The posterior arthroscopic portal site (green) will be located between the infraspinatus and teres minor muscles. (B) Anterior bursal view: The anterior arthroscopic portal site (red) will be located between the supraspinatus and subscapularis muscles. (C)–(E) Posterior articular view (from viewing perspective of the anterior portal): Approximately 2 cm² of the lateral joint capsule (C) under the infraspinatus will be resected from its humeral to glenoid insertions (D, dotted line), exposing the extra-articular rotator cuff muscles (E, colors as in Panel A) to the joint compartment. h = humeral head, g = glenoid, b = biceps tendon.</p

Biceps tendon and glenoid insertion.

<p>Longitudinal histologic sections from non-operated normal (A-C) and operated (D-G) animals (t = tendon; b = bone). The insertion of the non-operated animal showed the characteristic fibrocartilaginous transition zone with a well-defined tidemark and aligned chondrocytes (B, where B is a higher magnification of the region denoted by the left box on A). The adjacent tendon was characterized by parallel rows of tenocytes sandwiched between highly aligned collagen fibers (C, where C is a higher magnification of the region denoted by the right box on A). Ten weeks after posterior arthroscopic joint capsule injury, the tendon and its glenoid insertion showed reactive/reparative changes (D-G). The tendon in the operated animal (D) was thicker than normal (A). The distribution of chondrocytes at the tidemark was not uniform (E, where E is a higher magnification of the region denoted by the left box on D), and some foci showed few or no chondrocytes (white arrow) while others showed clustering of chondrocytes (black arrow), suggestive of proliferation. The tendon adjacent to the insertion showed villous hyperplasia (ampersand) and foci of marked hypervascularity (asterisk) (E). The rest of the tendon showed increased numbers of cells surrounded by basophilic ground substance (F, where F is a higher magnification of the region denoted by the middle box on D). There was marked hypervascularity along the entire length of the superior aspect of the tendon (G, where G is a higher magnification of the region denoted by the right box on D). Hematoxylin and eosin stain. Scale bar = 5mm (A, D), 500 microns (B, E), 200 microns (C, F, G).</p

Creation and surveillance of a posterior joint capsule injury, representative photographs from the left shoulder.

<p>(A) At index procedure, completion of the capsulectomy exposed the deep surface of the infraspinatus tendon and muscle, (B) At two weeks, there was negligible healing tissue present at the capsulectomy site. (C) At four weeks, the capsulectomy site appeared hemorrhagic and white, and thin fibrous tissue (arrows) was present. (B) At eight weeks, the deep surface of the infraspinatus tendon appeared yellow with fibrous tissue (arrows) originating medial to the glenoid rim and extending laterally to the deep surface of the tendon. i = infraspinatus tendon, h = humeral head articular surface, g = glenoid articular surface.</p

Necropsy findings at 10 weeks after the index procedure, representative images from the right shoulder.

<p>(A) Fibrovascular plaques were observed over the deep surface of the infraspinatus tendon (arrow), extending to the glenoid rim at the level of the scapular neck. (B) This material was thin, friable, and discontinuous (arrow), demonstrating that the capsular injury had remained patent. (C) The lateral infraspinatus muscle was edematous and its deep surface was covered with fibrovascular plaques laterally (arrow) and fibro-fatty tissue that encapsulated an accumulation of fluid medially (asterisk). (D) The deep surface of a non-operated normal canine infraspinatus tendon/muscle is shown for comparison. h = humeral head, g = glenoid, b = biceps tendon. Lines on C and D denote location of histologic sections of infraspinatus tendon (horizontal) and infraspinatus muscle (vertical).</p

Arthroscopic shoulder capsulectomy.

<p>(A) The animal was placed in a dorsal recumbent position with neck extension, and a forelimb suspension system was utilized to provide forelimb traction and ensure adequate glenohumeral joint distraction. (B) Arthroscopic posterior capsulectomy was performed with instrumentation in the posterior portal and the arthroscope in the anterior portal. (C) The humeral insertion of the intact posterior capsule visualized from the anterior portal (photo taken in a cadaver shoulder for clarity). The arrow denotes the insertion of the capsule at the supraspinatus/infraspinatus transition. (D) Removal of any remaining capsular tissue from the humeral or glenoid ends of the defect was done with an arthroscopic shaver (photo taken in a cadaver shoulder for clarity). a = anterior portal, c = joint capsule, h = humeral head articular surface, g = glenoid articular surface.</p

Identification of VHY/Dusp15 as a Regulator of Oligodendrocyte Differentiation through a Systematic Genomics Approach

<div><p>Multiple sclerosis (MS) is a neuroinflammatory disease characterized by a progressive loss of myelin and a failure of oligodendrocyte (OL)-mediated remyelination, particularly in the progressive phases of the disease. An improved understanding of the signaling mechanisms that control differentiation of OL precursors may lead to the identification of new therapeutic targets for remyelination in MS. About 100 mammalian Protein Tyrosine Phosphatases (PTPs) are known, many of which are involved in signaling both in health and disease. We have undertaken a systematic genomic approach to evaluate PTP gene activity in multiple sclerosis autopsies and in related <em>in vivo</em> and <em>in vitro</em> models of the disease. This effort led to the identification of Dusp15/VHY, a PTP previously believed to be expressed only in testis, as being transcriptionally regulated during OL differentiation and in MS lesions. Subsequent RNA interference studies revealed that Dusp15/VHY is a key regulator of OL differentiation. Finally, we identified PDGFR-beta and SNX6 as novel and specific Dusp15 substrates, providing an indication as to how this PTP might exert control over OL differentiation.</p> </div

PTPs the most strongly modulated during EAE in mice spinal cord and cerebellum.

<p>Number of PTP genes significantly modulated during the EAE time course in the spinal cord and in the cerebellum has been monitored and represented in two graphics. The number of PTP genes modulated increases dramatically over time. At day 28, the number of PTP genes modulated decreases until a basal level in cerebellum but remains high in the spinal cord. The highest fold changes in gene expression versus Sham animals have been reported in the table. Most of these PTPs have already been described in inflammatpry processes. Statistical analysis were performed using student <i>t-</i>test.</p

Clinical data of MS and control autopsies included in the study.

*<p><i>CWM</i>: Control white matter; <i>CGM</i>: Control gray matter; <i>NAWM</i>: Normal appearing white matter; <i>WML</i>: White matter lesioned; <i>NAGM</i>: Normal appearing gray matter; <i>GML</i>: Gray matter lesioned.</p

Identification of VHY potential substrates using phospho-peptides arrays.

<p>Each graphic correspond to the results expressed as optical density in arbitrary unites (a.u.) arising from two different arrays representing 720 different phospho-peptides. An arbitrary threshold allowed for the selection of the three phospho-peptides hits of each array namely (1) PDGFR-β (Platelet-derived Growth Factor Receptor beta); MK13 (MAPKinase 13/p38MAPKdelta); ATF2 (Activating Transcription Factor 2); SNX6 (Sorting Nexin 6); IF (Intrinsic factor); ErbB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3). Arrays were ran at pH6 with an enzyme concentration of 2 ng/mL.</p

Ten-point standardized rating scale for EAE clinical score monitoring.

<p>The final score for each animal is determined by the addition of all the above mentioned categories. Note: Score  =  15 for dead animal.</p