Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?

Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically to identify key factors of fetal regeneration. In addition, we compared the secretome of fetal ovine mesenchymal stem cells (MSCs) in vitro with injured fetal cartilage to identify potential MSC-derived therapeutic factors. Cartilage injury caused massive cellular changes in the synovial membrane, with macrophages dominating the fetal, and neutrophils the adult, synovial cellular infiltrate. Correspondingly, proteomics revealed differential regulation of pro- and anti-inflammatory mediators and growth-factors between adult and fetal joints. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult compared to fetal cartilage following injury. In contrast, several immunomodulating proteins and growth factors were expressed significantly higher in the fetus than the adult. Comparison of the in vitro MSCs proteome with the in vivo fetal regenerative signature revealed shared upregulation of 17 proteins, suggesting their therapeutic potential. Biomimicry of the fetal paracrine signature to reprogram macrophages and modulate inflammation could be an important future research direction for developing novel therapeutics.

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: "a macrophage niche". These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

Rapamycin-Induced Autophagy Promotes the Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells in the Temporomandibular Joint in Response to IL-1ß.

Cartilage defects in temporomandibular disorders (TMD) lead to chronic pain and seldom heal. Synovium-derived mesenchymal stem cells (SMSCs) exhibit superior chondrogenesis and have become promising seed cells for cartilage tissue engineering. However, local inflammatory conditions that affect the repair of articular cartilage by SMSCs present a challenge, and the specific mechanism through which the function remains unclear. Thus, it is important to explore the chondrogenesis of SMSCs under inflammatory conditions of TMD such that they can be used more effectively in clinical treatment. In this study, we obtained SMSCs from TMD patients with severe cartilage injuries. In response to stimulation with IL-1ß, which is well known as one of the most prevalent cytokines in TMD, MMP13 expression increased, while that of SOX9, aggrecan, and collagen II decreased during chondrogenic differentiation. At the same time, IL-1ß upregulated the expression of mTOR and decreased the ratio of LC3-II/LC3-I and the formation of autophagosomes. Further study revealed that rapamycin pretreatment promoted the migration of SMSCs and the expression of chondrogenesis-related markers in the presence of IL-1ß by inducing autophagy. 3-Benzyl-5-((2-nitrophenoxy)methyl)-dihydrofuran-2(3H)-one (3BDO), a new activator of mTOR, inhibited autophagy and increased the expression of p-GSK3ßser9 and ß-catenin, simulating the effect of IL-1ß stimulation. Furthermore, rapamycin reduced the expression of mTOR, whereas the promotion of LC3-II/LC3-I was blocked by the GSK3ß inhibitor TWS119. Taken together, these results indicate that rapamycin enhances the chondrogenesis of SMSCs by inducing autophagy, and GSK3ß may be an important regulator in the process of rapamycin-induced autophagy. Thus, inducing autophagy may be a useful approach in the chondrogenic differentiation of SMSCs in the inflammatory microenvironment and may represent a novel TMD treatment.

Comportamiento de pacientes con plica sinovial de la rodilla / Behavior of patients with knee plica synovialis

Fundamento: la plica sinovial de la rodilla es una de las causas de dolor anterior, se presenta de forma asilada o combinada a otras afecciones intrarticulares. El tratamiento quirúrgico mediante la vía artroscópica es el más usado en la actualidad. Objetivo: evaluar los resultados del tratamiento artroscópico en pacientes con plica sinovial. Métodos: se realizó un estudio observacional analítico con un nivel de evidencia III recomendación C en 181 pacientes con el diagnóstico clínico, imagenológico y artroscópico de plica sinovial en el Hospital Universitario Manuel Ascunce Domenech desde el 1 de enero de 2012 al 31 de enero de 2018. La población de estudio estuvo dada por todos aquellos enfermos en que se confirmó la presencia de plica sinovial patológica mediante la vía artroscópica, edad de 18 años o más y respuesta limitada o nula al tratamiento conservador ambulatorio por más de seis semanas. Resultados: el promedio de edad de los pacientes estudiados fue de 45,5 años, la razón sexo femenino-masculino fue de 1,9 a 1. Predominó la plica mediopatelar. Las lesiones de cartílago grados III/IV fueron las más encontradas, así como la afección monocompartimental patelofemoral. El desbridamiento y la meniscectomía fueron los procedimientos artroscópicos más realizados después de la sección de la plica. La respuesta clínica de los pacientes a los seis meses fue satisfactoria. Conclusiones: el tratamiento artroscópico de la plica sinovial es efectivo, en especial para pacientes con ausencia de otras lesiones intrarticulares(AU)

Background: knee plica synovialis is a common cause of anterior knee pain; it could show up isolated or associated to other intra-articular conditions. Nowadays, the surgical arthroscopic treatment is the most used way. Objective: the objective of this study was to evaluate the arthroscopic treatment in patients with plica synovialis of the knee. Methods: an analytic and observational study, with a level of evidence 3, recommendation C was performed in 181 patients with the clinical diagnosis of plica synovialis of the knee according to clinical, imaging and arthroscopic criteria in the provincial teaching hospital Manuel Ascunce Domenech in Camaguey city from January 1st, 2012 to January 31th, 2018. The population of the research was the amount of patients who had had the confirmation of having pathologycal plica synovialis through the arthroscopic way, 18 year-old patients and over and also limited or non-response to conservative ambulatory treatment for more than six weeks. Results: the average age was 45,5 years, female-male ratio was 1,9 to 1. The plica synovialis mediopatellaris prevailed. Cartilage lesions levels 3 and 4 were the most found as well as mono-compartiment affecting patellofemoral joint. Debridement and meniscectomy were the most common used arthroscopic procedures after plica section. Clinical results were good at six months.Conclusions: the arthroscopic treatment of plica synovialis is effective, especially in patients with absence of other intrarticular conditions(AU)

Use of positive contrast radiography to identify synovial involvement in horses with traumatic limb wounds.

BACKGROUND: The diagnostic value of positive contrast radiography in the work-up of suspected synovial infection in horses with limb wounds near synovial structures has yet to be systematically evaluated. OBJECTIVES: To determine the specificity, sensitivity and positive and negative predictive values of positive contrast radiography for identification of synovial infection in a population of horses with limb wounds. STUDY DESIGN: Retrospective case study comparing the performance of positive contrast radiography to the gold standard of synovial fluid cytology in horses presenting with limb wounds in the vicinity of synovial structures. METHODS: Case records of horses presenting to the Royal Veterinary College Equine Hospital between 2010 and 2015 with limb wounds that may have compromised adjacent synovial structures were analysed. Synovial fluid cytology results were used to categorise synovial structures in infected and noninfected groups. Positive contrast radiography results were compared between infected and noninfected groups and sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Fifty horses with 66 synovial structures were included in the study. Positive contrast radiography had a high specificity (86.4%), but only a moderate sensitivity (59.1%) for the identification of synovial infection. In addition, a low positive predictive value (68.4%) and high negative predictive value (80.9%) were observed in this population of horses. MAIN LIMITATIONS: Sensitivity, specificity and predictive values may differ between different synovial structures and cases. Different conclusions may be drawn from the results in a single population. Sensitivity and specificity of positive contrast radiography may also be influenced by different techniques used by examiners and by inherent characteristics of individual cases. CONCLUSIONS: Positive contrast radiography should be used for the investigation of potential synovial infection in horses with limb wounds, particularly if no synovial fluid sample for laboratory analysis can be obtained. However, it appears that positive contrast radiography is best used in combination with other tests to ensure that a correct and timely diagnosis is made.

[Ramp lesions : Tips and tricks in diagnostics and therapy]. / Rampenläsionen : Tipps und Tricks in Diagnostik und Therapie.

There is an increasing biomechanical and anatomical understanding of the different types of meniscal lesions. Lesions of the posterior part of the medial meniscus in the meniscosynovial area have recently received increased attention. They generally occur in association with anterior cruciate ligament (ACL) injuries. They are often missed ("hidden lesions") due to the fact that they cannot be seen by routine anterior arthroscopic inspection. Furthermore, meniscosynovial lesions play a role in anteroposterior knee laxity and, as such, they may be a cause of failure of ACL reconstruction or of postoperative persistent laxity. Little information is available regarding their cause with respect to injury mechanism, natural history, biomechanical implications, healing potential and treatment options. This article presents an overview of the currently available knowledge of these ramp lesions, their possible pathomechanism, classification, biomechanical relevance as well as repair techniques.

Indications for Hip Arthroscopy.

CONTEXT: Hip arthroscopy is gaining popularity within the field of orthopaedic surgery. The development and innovation of hip-specific arthroscopic instrumentation and improved techniques has resulted in improved access to the hip joint and ability to treat various hip pathologies. EVIDENCE ACQUISITION: Electronic databases, including PubMed and MEDLINE, were queried for articles relating to hip arthroscopy indications (1930-2017). STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Initially used as a technique for loose body removal, drainage/debridement of septic arthritis, and treatment of pediatric hip disorders, hip arthroscopy is currently used to treat various hip conditions. The recognition of femoroacetabular impingement (FAI) as a source of hip pain in young adults has rapidly expanded hip arthroscopy by applying the principles of osseous correction that were previously described and demonstrated via an open surgical dislocation approach. Hip pathologies can be divided into central compartment, peripheral compartment, peritrochanteric space, and subgluteal space disorders. CONCLUSION: Although hip arthroscopy is a minimally invasive procedure that may offer decreased morbidity, diminished risk of neurovascular injury, and shorter recovery periods compared with traditional open exposures to the hip, it is important to understand the appropriate patient selection and indications.

Joint morphogenetic cells in the adult mammalian synovium.

The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life.

Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.

BACKGROUND: Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. RESULTS: A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. CONCLUSIONS: A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial measurements of plasma SAA could potentially be used as an additional inexpensive, quick and easy tool for monitoring the treatment response in otherwise healthy horses presented with injuries penetrating synovial structures. However further studies will be necessary to ascertain its clinical utility.

Running Injuries: The Infrapatellar Fat Pad and Plica Injuries.

When considering knee pain in runners, clinicians differentiate sources of symptoms and determine their cause. Knee problems arise when a runner increases the amount/frequency of the loading through the lower limb. The way the loading is distributed through the knee determines which tissues are abnormally loaded. Knee problems cannot be considered in isolation, requiring a thorough investigation of static and dynamic lower limb mechanics, and footwear and surfaces. This article examines potential sources of knee pain and explores the role of the infrapatellar fat pad and synovial plica in the mechanics of the knee and its involvement in knee symptoms.

[Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial membranes]. / Bildgebung des Ellenbogengelenks mit Fokus MRT. Teil 2: Muskeln, Nerven und Synovia.

This review article discusses the magnetic resonance imaging (MRI) features and pathological changes of muscles, nerves and the synovial lining of the elbow joint. Typical imaging findings are illustrated and discussed. In addition, the cross-sectional anatomy and anatomical variants, such as accessory muscles and plicae are discussed. Injuries of the muscles surrounding the elbow joint, as well as chronic irritation are particularly common in athletes. Morphological changes in MRI, for example tennis or golfer's elbow are typical and often groundbreaking. By adapting the examination sequences, imaging planes and slices, complete and incomplete tendon ruptures can be reliably diagnosed. Although the clinical and electrophysiological examinations form the basis for the diagnosis of peripheral neuropathies, MRI provides useful additional information about the precise localization due to its high resolution and good soft tissue contrast and helps to rule out differential diagnoses. Synovial diseases, such as inflammatory arthritis, proliferative diseases and also impinging plicae must be considered in the MRI diagnostics of the elbow joint.

Changes of early post-traumatic osteoarthritis in an ovine model of simulated ACL reconstruction are associated with transient acute post-injury synovial inflammation and tissue catabolism.

The study described here tested the hypothesis that early intra-articular inflammation is associated with the development of post-traumatic osteoarthritis (PTOA) in a sheep model. We extended previously published work in which we investigated joint gross morphology and synovial mRNA expression of inflammatory and catabolic molecules 2 weeks after anatomic Anterior cruciate ligament (ACL) autograft reconstructive surgery (ACL-R). The same variables have been analyzed at 20 weeks post surgery together with new experimental variables at both time points. Animals were sacrificed at 20 weeks post ACL-R surgery and their joints graded for signs of PTOA. Synovial samples were harvested for histological grading plus mRNA and protein analysis for a panel of inflammatory and catabolic molecules. The mRNA expression levels for this panel plus connective tissue matrix turnover molecules were also investigated in cartilage samples. Results of gross morphological assessments at 20 weeks post surgery showed some changes consistent with early OA, but indicated little progression of damage from the 2 week time point. While significant alterations in mRNA levels for synovial inflammatory and catabolic molecules were detected at 2 weeks, values had normalized by 20 weeks. Similarly, all mRNA expression levels for inflammatory and catabolic molecules in articular cartilage had returned to normal levels by 20 weeks post ACL-R surgery. We conclude that synovial inflammatory processes are initiated very early after ACL-R surgery and may instigate events that lead to the gross cartilage and joint abnormalities observed as early as 2 weeks. However, the absence of sustained inflammation and joint instability may prevent OA progression.

Cellular apoptosis and proliferation in the middle and late intrasynovial tendon healing periods.

PURPOSE: Cellular apoptosis might be an important molecular event in the middle or late healing periods of intrasynovial tendons, but this has not been studied. We aimed to investigate cellular apoptosis and corresponding cellular proliferation in the middle and late healing stages of intrasynovial tendons. METHODS: The flexor digitorum profundus tendons of 48 long toes (24 chickens) were completely transected within the sheath region and were repaired surgically. At days 28, 42, 56, and 84 after surgery, tendons were harvested and sectioned. In situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to detect apoptotic cells. The sections were stained immunofluorescently with antibodies to proliferating cell nuclear antigen to assess proliferation and to Bcl-2 (an anti-apoptotic protein). Positively stained tenocytes were counted, and their distributional differences were verified in 3-dimensional images. RESULTS: The repaired intrasynovial tendons exhibited generally greater apoptosis in the surface region than in the core. The differences were more remarkable in the extended region than in the junction region of the cut tendon. At the core of the junction site, apoptosis of tenocytes was pronounced at all time points, but it was less severe at the core of the extended region. The proliferating cell nuclear antigen-positive and Bcl-2-positive tenocytes decreased significantly and continually at days 28, 42, and 56, respectively; these tenocytes were at a minimum at days 56 and 84. CONCLUSIONS: Apoptotic changes of tenocytes are most marked in the surface region and in the junction region of the healing tendon in the middle and late healing stages. Apoptosis in the core is less dramatic compared to that in the surface in the extended tendon regions. Cellular proliferation declines drastically and is minimal at days 56 and 84. CLINICAL RELEVANCE: Tenocyte apoptosis in the middle and late stages might be an important event contributing to intrasynovial tendon remodeling, which affects the healing strength and formation of adhesions.

Suction drainage influence on knee effusion following partial meniscectomy with partial fat pad or synovium resection.

OBJECTIVE: The aim of our study was to examine the effect of suction drains on knee after arthroscopic partial meniscectomy with partial fat pad removal or synovectomy. METHODS: We performed arthroscopic partial meniscectomy for posterior tears of the medial meniscus and partial fat pad or synovium shaving in 72 patients. Following surgery, a suction drain was not used in 40 patients (Group A) and used in 32 (Group B). Both groups were similar in terms of age, gender, and total operation time. The patients were evaluated at 1, 2, and 4 weeks postoperatively for the presence of a knee effusion. RESULTS: No significant difference was observed in the grade of effusion and the average percent change in the effusion grade between Groups A and B at 1, 2, and 4 weeks postoperatively. CONCLUSION: Use of a suction drain did not influence the postoperative effusion or the clinical course of the effusion after arthroscopic partial meniscectomy with partial fat pad removal or synovectomy.

Inflamación sinovial en un modelo experimental de síndrome metabólico en conejo / Synovial inflammation in an experimental model of metabolic syndrome in the rabbit

Objetivo: Analizar el efecto del síndrome metabólico (SM) sobre la inflamación sinovial en un modelo experimental en conejo. Material y métodos: Se probaron tres intervenciones dietéticas diferentes para inducir un modelo experimental de SM, en 21 conejos New Zealand hembra, de 8 meses de edad: 1) alimentación con dieta enriquecida con 1% de colesterol y 3% de aceite de cacahuete y agua ad libitum; 2) alimentación con dieta normal y agua con 30% de fructosa ad libitum; 3) alimentación con dieta enriquecida con 1% de colesterol y 3% de aceite de cacahuete y agua con 30% de fructosa ad limitum. Los animales se dejaron evolucionar durante 12 semanas y se hizo un seguimiento semanal de peso, glucosa basal, colesterol HDL, triglicéridos. Tras el sacrificio, se tomaron muestras de membrana sinovial para cuantificar el infiltrado macrofágico sinovial mediante inmunohistoquímica. Resultados: La única intervención dietética con la que conseguimos inducir alteraciones asociadas al SM en los conejos fue alimentándolos con una dieta hiperlipémica. Estos animales, además de presentar hiperglucemia y dislipemia, tenían un infiltrado macrofágico sinovial mayor que el del grupo control. Conclusión: La alimentación con dieta hiperlipémica induce alteraciones típicas del SM en el conejo, acompañadas de un aumento del infiltrado macrofágico sinovial, lo que sugiere que el macrófago podría desempeñar un papel importante en el inicio y/o la progresión de la artrosis descrita que se asocia con el SM (AU)

Objetive: To analyze the effect of metabolic syndrome (MS) upon synovial inflammation in an experimental model in the rabbit. Material and methodology: Three different diets were used to induce an experimental model of MS in 21 female New Zealand rabbits (aged 8 months): 1) diet enriched with 1% cholesterol and 3% peanut oil, with water, ad libitum; 2) normal diet, with water, and 30% fructose, ad libitum; 3) diet enriched with 1% cholesterol and 3% peanut oil, with water, and 30% fructose, ad libitum. The animals were followed-up on for 12 weeks, with weekly monitoring of body weight, basal glucose, HDL-cholesterol and triglycerides. Following sacrifice, synovial membrane samples were collected to quantify the synovial macrophage infiltrate using immunohistochemical techniques. Results: The only diet to induce alterations associated with MS in the rabbits was the hyperlipidemic diet. These animals, in addition to presenting hyperglycemia and dyslipidemia, showed greater synovial macrophage infiltration than the control group. Conclusion: A hyperlipidemic diet induces alterations typical of MS in the rabbit, accompanied by an increase in synovial macrophage infiltration (AU)

Anterior knee pain in the young athlete: diagnosis and treatment.

The underlying etiology of anterior knee pain has been extensively studied. Despite many possible causes, often times the diagnosis is elusive. The most common causes in the young athlete are osteosynchondroses, patellar peritendinitis and tendinosis, synovial impingement, malalignment, and patellar instability. Less common causes are osteochondritis dissecans and tumors. It is always important to rule out underlying hip pathology and infections. When a diagnosis cannot be established, the patient is usually labeled as having idiopathic anterior knee pain. A careful history and physical examination can point to the correct diagnosis in the majority of cases. For most of these conditions, treatment is typically nonoperative with surgery reserved for refractory pain for an established diagnosis.

Synovial folds - a pain in the neck?

The synovial folds of the cervical spine are regarded as a potential source of neck pain and headache, especially following whiplash injury. Damage to the synovial folds following motor vehicle trauma has been well documented in post-mortem studies. However, methods of identifying injury to the synovial folds in the survivors of motor vehicle trauma have proven elusive to date. Recently, it has been made possible to image the synovial folds in vivo using magnetic resonance imaging. This now makes it feasible to investigate the potential involvement of synovial folds in the generation of neck pain and headache and its relief using spinal manipulation. This paper reviews critically the morphology of the synovial folds of the cervical spine that underpins the hypotheses proposed to explain their functional and clinical significance and a new system of naming and classifying the synovial folds is presented. Although there is some evidence to support the contribution of the synovial folds to neck pain, several theories have little or no support and require investigation and further evaluation. These findings have implications for understanding the anatomical basis of neck pain and headache and the rationale for the use of spinal manipulation in their management.

Finite element model of subsynovial connective tissue deformation due to tendon excursion in the human carpal tunnel.

Carpal tunnel syndrome (CTS) is a nerve entrapment disease, which has been extensively studied by the engineering and medical community. Although the direct cause is unknown, in vivo and in vitro medical research has shown that tendon excursion creates microtears in the subsynovial connective tissue (SSCT) surrounding the tendon in the carpal tunnel. One proposed mechanism for the SSCT injury is shearing, which is believed to cause fibrosis of the SSCT. Few studies have reported quantitative observations of SSCT response to mechanical loading. Our proposed model is a 2-D section that consists of an FDS tendon, interstitial SSCT and adjacent stationary tendons. We believe that developing this model will allow the most complete quantitative observations of SSCT response to mechanical loading reported thus far. Boundary conditions were applied to the FEA model to simulate single finger flexion. A velocity was applied to the FDS tendon in the model to match loading conditions of the documented cadaver wrist kinematics studies. The cadaveric and FEA displacement results were compared to investigate the magnitude of stiffness required for the SSCT section of the model. The relative motions between the model and cadavers matched more closely than the absolute displacements. Since cadaveric models do not allow identification of the SSCT layers, an FEA model will help determine the displacement and stress experienced by each SSCT layer. Thus, we believe this conceptual model is a first step in understanding how the SSCT layers are recruited during tendon excursion.