Geoffroy Nourissat

Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen. Here, we investigated the function of the zinc finger transcription factor EGR1 in tendon formation, healing, and repair using rodent animal models and mesenchymal stem cells (MSCs). Adult tendons of Egr1-/- mice displayed a deficiency in the expression of tendon genes, including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo. Egr1 was required for the normal gene response following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1 expression programmed MSCs toward the tendon lineage and promoted the formation of in vitro-engineered tendons from MSCs. The application of EGR1-producing MSCs increased the formation of tendon-like tissues in a rat model of Achilles tendon injury. We provide evidence that the ability of EGR1 to promote tendon differentiation is partially mediated by TGF-β2. This study demonstrates EGR1 involvement in adult tendon formation, healing, and repair and identifies Egr1 as a putative target in tendon repair strategies.

Tendon injury: from biology to tendon repair.

Tendon is a crucial component of the musculoskeletal system. Tendons connect muscle to bone and transmit forces to produce motion. Chronic and acute tendon injuries are very common and result in considerable pain and disability. The management of tendon injuries remains a challenge for clinicians. Effective treatments for tendon injuries are lacking because the understanding of tendon biology lags behind that of the other components of the musculoskeletal system. Animal and cellular models have been developed to study tendon-cell differentiation and tendon repair following injury. These studies have highlighted specific growth factors and transcription factors involved in tenogenesis during developmental and repair processes. Mechanical factors also seem to be essential for tendon development, homeostasis and repair. Mechanical signals are transduced via molecular signalling pathways that trigger adaptive responses in the tendon. Understanding the links between the mechanical and biological parameters involved in tendon development, homeostasis and repair is prerequisite for the identification of effective treatments for chronic and acute tendon injuries.

Induction of the chemokine IL-8/Kc by the articular cartilage: Possible influence on osteoarthritis

PURPOSE IL-8 and its murine equivalent keratinocyte chemoattractant (Kc), chemokines produced by chondrocytes, contribute to the pathophysiology of osteoarthritis. However, the mechanisms leading to their production are poorly known. We aimed to investigate whether mechanical (compression), inflammatory (IL-1β) and metabolic (visfatin) stresses may induce the release of Kc when applied on murine cartilage. METHODS Mouse cartilage explants were subjected to intermittent compression for 4, 6 and 24h. Primary cultures of immature murine articular chondrocytes were obtained by enzymatic digestion of articular cartilage from 6-days-old newborns mice. The effect of compression, IL-1β (10, 50, 100pg/mL) and of visfatin (5μg/mL) on the release of Kc was assessed by ELISA. IL-8 levels in conditioned media from human OA joint tissues (cartilage or synovium) were also assessed. RESULTS In comparison with non-compressed explants, loading increased Kc release of 3.2-, 1.9- and 2.0-fold at 4, 6 and 24h respectively (P<0.004, n=9). IL-1β triggered an increase of Kc release by primary cultured chondrocytes of 4.1-, 15.5- and 35.2-fold at 10, 50 and 100pg/mL of IL-1β respectively (P<0.05, n=4). Likewise, visfatin (5μg/mL) induced an increase in Kc release of 56.5±25.2 fold (P=0.002, n=6). IL-8 was released in conditioned media by synovium as well as by cartilage. CONCLUSION We show for the first time that IL-8/Kc is highly responsive to mechanical, inflammatory and metabolic stresses, strengthening the hypothesis that IL-8/Kc could be added to the cytokines which may have a deleterious impact in osteoarthritis.

Penetrating Volar Injuries of the Hand: Diagnostic Accuracy of US in Depicting Soft-Tissue Lesions

PURPOSE To evaluate the effectiveness of ultrasonography (US) in depicting lesions of the tendons, arteries, and nerves caused by penetrating wounds of the volar aspect of the hand, with surgical exploration as the reference standard. MATERIALS AND METHODS Consecutive patients seen at one center over a 2-month period in 2006 were prospectively included. The institutional review board approved the study, and each patient gave written informed consent. There were 30 injuries in 26 patients (19 men and seven women; median age, 34 years). US examination was performed before surgery. Surgeons were not informed of the US findings. For tendons, arteries, and nerves, the sensitivity, specificity, positive predictive value, and negative predictive value of US were computed. RESULTS US depicted all tendon lesions, with no false-positive findings; two arterial lesions were missed, with no false-positive findings, and four nerve lesions were missed, with six false-positive findings. The negative predictive value was 100% (95% confidence interval: 95.5%, 100%) for tendons, 96.7% (95% confidence interval: 88.7%, 99.6%) for arteries, and 93.7% (95% confidence interval: 84.5%, 98.2%) for nerves. In three cases, US depicted foreign bodies missed at surgery. CONCLUSION US was highly effective in identifying patients with no tendon or arterial lesions. Performance was poorer for diagnosing nerve lesions. US followed by a repeat physical examination after 72 hours to look for missed nerve damage may deserve evaluation as an alternative to routine surgical exploration when US findings are normal.

Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption

Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.

Diagnostic préopératoire des anses de seau méniscales : valeur des critères cliniques, arthro-TDM et IRM: À propos d’une série de 33 cas confirmés par arthroscopie

Resume L’objectif de cette etude etait d’analyser la pertinence des signes cliniques et l’apport des nouvelles modalites d’imagerie en coupe (arthro-TDM et IRM) pour le diagnostic preoperatoire d’un type de lesions meniscales longitudinales dites en anse de seau. Il s’agit d’une serie retrospective de 33 lesions meniscales en anse de seau confirmees arthroscopiquement, ayant beneficie d’un bilan preoperatoire comportant une arthrographie et/ou un arthro-TDM et/ou une IRM. Les examens ont ete relus par 2 radiologues seniors en consensus. Les principaux signes cliniques recherches etaient des antecedents de blocage typique et l’existence d’un flessum preoperatoire. Les signes radiologiques etudies correspondaient a la visualisation du fragment deplace, en coupe coronale (fragment dans l’echancrure) ou sagittale (megacorne anterieure, double LCP, signe du serpent). Les antecedents de blocage typique etaient retrouves 14 fois et un flessum 15 fois. Seuls 10 patients presentaient l’association evocatrice « blocage + flessum ». Le diagnostic positif de lesion meniscale en anse de seau etait porte en IRM (13/15), en arthro-TDM (6/7) et en arthrographie (10/24), soit une sensibilite equivalente pour les 2 techniques d’imagerie en coupe. Le signe du fragment dans l’echancrure en coupe coronale est un signe constant. Le signe du double LCP est un signe sensible pour les lesions du menisque medial et pour les lesions du menisque lateral en cas de rupture associee du LCA. 9 patients avaient eu plusieurs examens (n = 2 ou 3) et aucun faux negatif n’etait retrouve dans ce groupe. Dans 9 cas, le diagnostic d’anse de seau n’avait pas ete porte (Arthrographie : n = 7 ; IRM : n = 2). Dans ces cas, on peut incriminer l’etroitesse du fragment meniscal et parfois le delai entre le bilan et l’arthroscopie.PURPOSE OF THE STUDY It is important for both the patient and the surgeon to determine whether a meniscal lesion can be repaired before undertaking surgery. The purpose of this study was to examine the pertinence of clinical signs and determine the value of imaging findings for the preoperative diagnosis of bucket-handle meniscal tears. This preliminary study was conducted before undertaking an analysis of preoperative criteria of reparability in a homogeneous group of meniscal lesions. MATERIAL AND METHODS This retrospective series included 33 arthroscopically-proven bucket-handle meniscal tears in patients who underwent arthrography and/or arthroscan and/or MRI preoperatively. The images were reviewed by two senior radiologists who established a consensus diagnosis. Clinically, the type of blockage and the presence of permanent flexion before surgery were noted. The following items were noted on the imaging results: fragment displacement (fragment in the notch on the coronal slice) anterior megahorn, double PCL, and serpent sign on the sagittal slice. Longitudinal, transversal extension and position of the bucket-handle were noted. We searched for correlations with the intraoperative findings. RESULTS Fourteen patients had a history of knee blocking and 15 had permanent flexion before surgery. Only 10 patients had the typical association of blocking and flexion. Certain diagnosis of bucket-handle meniscal tear was provided by MRI (13/15), arthroscan (6/7), and arthrography (10/24) giving an equivalent sensitivity for the two slice imaging techniques. The sign of a fragment in the notch on the coronal slice was a constant finding. The double PCL sign was sensitive for medial meniscal tears and for lateral meniscal tears with associated ACL tears. The diagnosis was successfully established in all 9 patients who underwent several explorations (2 or 3). Buckle-handle meniscal tear was not identified in 9 patients (arthrography 7, MRI 2). DISCUSSION Our findings demonstrate that the preoperative diagnosis of bucket-handle meniscal tears cannot be properly established on clinical criteria of typical blocking and/or permanent flexion. They confirm that arthrography is not contributive to diagnosis and that the absence of a slice image is detrimental to diagnosis. The sensitivity of the two slice imaging methods was similar. The key sign was the presence of a fragment in the notch on the coronal slice; in the three cases where this sign was absent, the reason was found to be the small size of the displaced fragment (resolution limit) and time between imaging and arthroscopy. The characteristic features of the bucket-handle lesions observed in this series are exactly the same as reported in earlier reports but to our knowledge provide the first data on comparative performance of arthroscan and MRI. CONCLUSION The noninvasive nature of MRI and the possibility of assessing the meniscal wall and the quality of the meniscal tissue make MRI the exploration of choice for preoperative assessment of meniscal tears.

Cardiometabolic risk factors in primary centred and rotator cuff-related shoulder osteoarthritis: a comparative study

Background Risk factors for shoulder osteoarthritis (SOA) have been poorly studied. SOA has two anatomical subtypes: primary centred SOA (centred SOA) and rotator cuff-related OA (non-centred SOA). We examined whether cardiometabolic risk factors are preferentially associated with centred than mechanical-induced non-centred SOA. Methods This 2004–2012 retrospective multicentric study included patients with SOA. Data on clinical characteristics, especially cardiometabolic risk factors, were collected. We compared patients with radiographic-centred and non-centred SOA and tested the association between cardiometabolic risk factors and subtypes of SOA. Results We included 147 patients (101 women (68.7%); mean age 75.8±10 years); 99 had centred SOA. As compared with patients with non-centred SOA, those with centred SOA were older (77.5±9 vs 72.4±11 years; p=0.004) with no difference in cardiometabolic disturbances or their accumulation. Multivariable analyses indicated that older age was independently associated with centred SOA (OR 1.06;95% CI 1.02 to 1.1; p=0.004), and cardiovascular diseases were less associated with this subtype (OR 0.27; 95% CI 0.089 to 0.824; p=0.02) than with the non-centred one. Conclusion Cardiometabolic risk factors were not more prevalent with primary centred than rotator cuff-related SOA. They may participate in the pathophysiology of both SOA subtypes through cartilage and tendon disruption.

Return to Sport After Shoulder Arthroplasty in Recreational Athletes: A Systematic Review and Meta-analysis

Background: One of the most frequent demands from patients after shoulder replacement surgery is to return to sport. Purpose: To determine the rate of return to sport after shoulder arthroplasty (total shoulder arthroplasty, reverse shoulder arthroplasty, hemiarthroplasty) in recreational athletes. Study Design: Meta-analysis and systematic review. Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to perform this systematic review and meta-analysis of the results in the literature as well as the presentation of results. A search of the literature was performed in the electronic databases MEDLINE, Scopus, Embase, and the Cochrane Library. The quality of the included studies was evaluated according to the MINORS (Methodological Index for Nonrandomized Studies) score. Inclusion criteria were studies in English evaluating return to sport after shoulder replacement surgery and on patients practicing a sport regularly, whatever the level, with all ages and sports included. The main criterion was the rate of patients who returned to a sport activity. Results: Nine studies were selected among the 35 identified, including a total of 613 patients (39% male and 61% female) with a mean age of 71.7 years (range, 22.6-92.6 years). All the included patients practiced sports before surgery. The most common reported sports were golf (n = 140), swimming (n = 128), and tennis (n = 54). The mean rate of return to sport was 80.7% (range, 57.1%-97.3%). All patients who returned to sport were practicing in the 3 months before surgery. No radiological data were reported in the literature. The subgroup analysis for resuming golf after shoulder arthroplasty revealed a rate of return to sport of 79.2% (95% CI, 62.9%-89.5%). In the swimming subgroup, the rate was 75.6% (95% CI, 61.3%-85.8%) and in the tennis subgroup was 63.5% (95% CI, 34.1%-85.5%). The subgroup analysis for reverse shoulder arthroplasty reported a lower rate of return to sport than for all types of shoulder arthroplasty combined: 76.5% (95% CI, 60%-87%) versus 80.7% (95% CI, 70.9%-87.8%), respectively. Conclusion: Most patients returned to sport after surgery, and all who returned to sport were practicing their sport in the 3 months before surgery. No radiological data were reported in the literature.

Os Acromiale in Professional Tennis Players

Background: Os acromiale is a rare condition mostly reported in the literature through case reports, imaging studies, or reports of surgical treatment. This condition is the result of nonunion of growth plates of the acromion during the natural developmental process that occurs between 15 and 25 years of age. Its incidence is low, and few studies are available in the literature on athletes with high functional demands, and particularly on athletes within a specific sport. Purpose: To collect epidemiological data and to report the amount of time out of play as well as the type of treatment and its efficiency in professional tennis players. Study Design: Case series; Level of evidence, 4. Methods: We performed a retrospective study using the medical data of athletes within our national tennis league who complained about their shoulder between 2011 and 2016. Nine professional tennis players (mean age, 20 years) with painful shoulders were diagnosed with os acromiale; 3 of them played at an international level, with the other 6 playing at a national level. The diagnosis was confirmed using radiography, including the axillary view, and magnetic resonance imaging (MRI). One female player had associated subacromial bursitis. Results: All cases of os acromiale were classified as involving the mesoacromion, following the Lieberson classification. No patient underwent surgery, and no patient was treated with local or subacromial infiltration. Patients stopped competition and training throughout the rehabilitation period. All patients received medical treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), ice, and physical therapy with a specific rehabilitation program. All athletes returned to their former level of play after a mean of 37 days. No patient suffered from recurrent pain. One patient underwent MRI after 2 years, showing a normal bone signal and complete healing of the acromion. Conclusion: Conservative treatment including NSAIDs, rest, ice, and physical therapy allowed for good recovery and return to the former level of play. Surgical treatment is usually not indicated for os acromiale in the professional tennis player.

Diagnosis of Ehlers-Danlos syndrome after a first shoulder dislocation

BACKGROUND Shoulder dislocation is often the first symptom of Ehlers-Danlos syndrome (EDS). Whether it occurs in early-onset EDS is unknown. In most cases, surgical failure leads to the diagnosis. We aimed to determine whether clinical symptoms can signal the presence of EDS at a first dislocation. MATERIALS AND METHODS In this retrospective study, we analyzed clinical and radiologic data for 27 patients with EDS and shoulder instability and a control population of 40 consecutive non-EDS patients undergoing surgery for an unstable shoulder. Data were collected on gender, age, single or bilateral disease, general hyperlaxity, shoulder hyperlaxity, number of dislocations or subluxations, nontraumatic onset, and pain specificity. Nerve and vascular injuries, joint disorders, and family history were recorded, and radiologic data were reported. RESULTS Age <14 years, female sex, bilateral disorder, and general hyperlaxity were significantly more frequent in patients with EDS and a first dislocation than in those without EDS. Painless dislocation with pain after dislocation and concomitant nerve injury were more frequent in affected patients, as were hemostasis disorders and a family history of joint hyperlaxity. Bone lesions were not seen on radiographs. Only the hyperlaxity sign (external rotation >85°) did not differ between the groups. CONCLUSION After a first dislocation in a young girl with global hyperlaxity but not necessarily shoulder hyperlaxity, painless atraumatic dislocation with pain after reduction can suggest EDS.