Treatment of Irreparable Rotator Cuff Tears: Superior Capsular Reconstruction with Fascia Lata Allograft / Tratamento das rupturas irreparáveis do manguito rotador: Reconstrução capsular superior com aloenxerto de fáscia lata

Abstract Objective The objective of the present study was to evaluate the efficacy and safety of superior capsular reconstruction (SCR) using fascia lata allograft. Methods A prospective case series of 15 patients with irreparable supraspinatus tear who underwent SCR using fascia lata allograft. The American Shoulder and Elbow Surgeons (ASES) scale at 12 months after surgery was the primary outcome. The University of California Los Angeles (UCLA), Constant-Murley, and Single Assessment Numeric Evaluation (SANE) scales, in addition to the range of motion, were secondary outcomes. Radiological parameters were also evaluated by simple radiographs and magnetic resonance imaging (MRI). Results Fifteen patients completed 12 months of postoperative follow-up. The ASES score increased from 34.0 to 73.0 (p= 0.005). The UCLA, Constant-Murley, and SANE scales also showed statistically significant differences (p= 0.001; p= 0.005; and p= 0.046). In the evaluation of range of motion, there was improvement in elevation and in external rotation (95 to 140°, p= 0.003; 30 to 60°, p= 0.007). Six patients (40%) had complete graft healing. The clinical outcomes were significantly higher in the patients who presented graft healing. Conclusions Superior capsular reconstruction using a fascia lata allograft is a safe and effective procedure in short follow-up. Level of Evidence IV; Therapeutic Study; Case Series.

Resumo Objetivo O objetivo do presente estudo foi avaliar a eficácia e a segurança da reconstrução capsular superior (RCS) com a utilização do aloenxerto de fáscia lata. Métodos Uma série de casos prospectivos de 15 pacientes com ruptura irreparável do supraespinhal foi submetida a RCS com aloenxerto de fáscia lata, sendo adotada como desfecho primário a escala American Shoulder and Elbow Surgeons (ASES, na sigla em inglês) aos 12 meses do pós-operatório. Como desfechos secundários, foram adotadas as escalas da University of California Los Angeles (UCLA, na sigla em inglês), Constant-Murley, e Single Assessment Numeric Evaluation (SANE, na sigla em inglês), além da amplitude de movimento. Os parâmetros radiológicos também foram avaliados por radiografias simples e ressonância magnética (RM). Resultados Quinze pacientes completaram 12 meses de acompanhamento pós-operatório. O escore ASES aumentou de 34,0 para 73,0 (p= 0,005). As escalas UCLA, Constant-Murley e SANE também apresentaram diferenças estatisticamente significativas (p= 0,001; p= 0,005; e p= 0,046). Na avaliação da amplitude de movimento, houve melhora na elevação e rotação externa (95 a 140°, p= 0,003; 30 a 60°, p= 0,007). Seis pacientes (40%) tiveram cicatrização completa do enxerto. Os desfechos clínicos foram significativamente maiores nos pacientes que apresentaram cicatrização do enxerto. Conclusões A RCS com aloenxerto de fáscia lata é um procedimento seguro e eficaz com um curto acompanhamento de tempo. Nível de evidência IV; Estudo Terapêutico; Série de casos.

Management of arthrofibrosis in neuromuscular disorders: a review.

Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.

Synovial Macrophages in Osteoarthritis: The Key to Understanding Pathogenesis?

Effective treatment of osteoarthritis (OA) remains a huge clinical challenge despite major research efforts. Different tissues and cell-types within the joint contribute to disease pathogenesis, and there is great heterogeneity between patients in terms of clinical features, genetic characteristics and responses to treatment. Inflammation and the most abundant immune cell type within the joint, macrophages, have now been recognised as possible players in disease development and progression. Here we discuss recent findings on the involvement of synovial inflammation and particularly the role of synovial macrophages in OA pathogenesis. Understanding macrophage involvement may hold the key for improved OA treatments.

Adverse Local Tissue Reactions are Common in Asymptomatic Individuals After Hip Resurfacing Arthroplasty: Interim Report from a Prospective Longitudinal Study.

BACKGROUND: The evaluation of the natural history prevalence of adverse local tissue reactions (ALTRs) using MRI has focused only on metal-on-metal (MoM) bearing surfaces without comparison to nonMoM bearing surfaces. QUESTIONS/PURPOSES: To determine (1) the longitudinal changes and differences in blood metal ion levels in patients with hip resurfacing arthroplasty (HRA), ceramic-on-ceramic (CoC) THA, and metal-on-polyethylene (MoP) THA compared with those undergoing ceramic-on-polyethylene (CoP) THA; (2) how the longitudinal change of synovial reaction classification in patients with HRA, CoC THA, and MoP THA compares with those undergoing CoP THA, and whether there is an association between the presence of an ALTR or metallosis on MRI with corresponding patient-reported outcomes, or the presence of capsular dehiscence; and (3) differences in blood metal ion levels between patients undergoing HRA with an ALTR or metallosis on MRI and those with HRA without these conditions. METHODS: Between March 2014 and February 2019, 22,723 patients underwent primary HRA and THA at one center. Patients received an HRA based on their desired athletic level after surgery and the presence of normal acetabular and proximal femoral bone morphology without osteopenia or osteoporosis. Two percent (342 of 22,723) of patients were contacted to participate, and 71% (243 of 342 hips in 206 patients) were enrolled for analysis at baseline. The patients underwent arthroplasty for degenerative joint disease, and 25 patients withdrew over the course of the study. We included patients who were more than 1 year postarthroplasty. All participants had an MRI examination and blood serum ion testing and completed a Hip Disability and Osteoarthritis Outcome Score survey annually for four years (baseline, year 1, year 2, year 3). Morphologic and susceptibility-reduced MR images were evaluated by a single radiologist not involved in the care of patients for the presence and classification of synovitis (Gwet AC1: 0.65 to 0.97), synovial thickness, and volume (coefficient of repeatability: 1.8 cm3). Linear mixed-effects models were used to compare the mean synovial thickness, synovial volume, and Hip Disability and Osteoarthritis Outcome Score subscales between bearing surfaces at each timepoint and within each bearing surface over time. Marginal Cox proportional hazards models were used to compare the time to and the risk of developing ALTR only, metallosis only, and ALTR or metallosis between bearing surfaces. All models were adjusted for age, sex, BMI, and length of implantation based on known confounders for hip arthroplasty. Adjustment for multiple comparisons was performed using the Dunnett-Hsu method. RESULTS: Patients with unilateral HRA had higher cobalt and chromium serum ion levels (baseline: 1.8 ± 0.8 ppb, year 1: 2.0 ± 1.5 ppb, year 2: 2.1 ± 1.2 ppb, year 3: 1.6 ± 0.7 ppb) than those with unilateral CoP bearings (baseline: 0.0 ± 0.1 ppb, year 1: 0.1 ± 0.3 ppb, year 2: 0.0 ± 0.2 ppb, year 3: 0.0 ± 0.0 ppb) at all timepoints (p < 0.001 for each time point). More patients who received an HRA developed ALTR or metallosis on MRI than did patients with CoP bearings (hazard ratio 4.8 [95% confidence interval 1.2 to 18.4]; p = 0.02). There was no association between the longitudinal change of synovial reaction to ALTR or metallosis on MRI with patient-reported outcomes. In addition, there was no association between the presence of dehiscence at baseline and the subsequent development of ALTR or metallosis, as seen on MRI. There were elevated cobalt (4.7 ± 3.5 ppb) and chromium (4.7 ± 2.6 ppb) serum levels in patients with unilateral HRA who had an ALTR or metallosis present on MRI at year 1 compared with patients without an ALTR or metallosis on MRI (cobalt: 1.8 ± 1.0 ppb, mean difference 4.7 ppb [95% CI 3.3 to 6.0]; p < 0.001; chromium: 2.3 ± 0.5 ppb, mean difference 3.6 ppb [95% CI 2.2 to 5.0]; p < 0.001) as well as for chromium at year 3 (3.9 ± 2.4 ppb versus 2.2 ± 1.1 ppb, mean difference 1.3 ppb [95% CI 0.3 to 2.4]; p = 0.01). CONCLUSION: We found a higher proportion of ALTR or metallosis on MRI in patients with HRA compared with patients with CoP, even when patient self-assessed symptomatology of those with an ALTR or metallosis on MRI was not different than the absence of these features. MRI detected ALTRs in high-function patients, emphasizing that an annual clinical assessment dependent on survey or blood ion testing alone may not detect soft tissue complications. The results of this study are in line with prior consensus recommendations of using MRI as part of a routine follow-up protocol for this patient population. LEVEL OF EVIDENCE: Level III, therapeutic study.

Inhibition of lipid phosphatase SHIP1 expands myeloid-derived suppressor cells and attenuates rheumatoid arthritis in mice.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease of unknown cause, characterized by infiltration and accumulation of activated immune cells in the synovial joints where cartilage and bone destructions occur. Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was shown to be involved in the regulation of MDSC differentiation. The purpose of the present study was to investigate the effect of inhibition of SHIP1 on the expansion of MDSCs in RA using a collagen-induced inflammatory arthritis (CIA) mouse model. In DBA/1 mice, treatment with a small molecule-specific SHIP1 inhibitor 3α-aminocholestane (3AC) induced a marked expansion of MDSCs in vivo. Both pretreatment with 3AC of DBA/1 mice prior to CIA induction and intervention with 3AC during CIA progression significantly reduced disease incidence and severity. Adoptive transfer of MDSCs isolated from 3AC-treated mice, but not naïve MDSCs from normal mice, into CIA mice significantly reduced disease incidence and severity, indicating that the 3AC-induced MDSCs were the cellular mediators of the observed amelioration of the disease. In conclusion, inhibition of SHIP1 expands MDSCs in vivo and attenuates development of CIA in mice. Small molecule-specific inhibition of SHIP1 may therefore offer therapeutic benefit to patients with RA and other autoimmune diseases.

Tetrandrine inhibits the occurrence and development of frozen shoulder by inhibiting inflammation, angiogenesis, and fibrosis.

BACKGROUND: Frozen shoulders (FS) is a major clinical concern, where chronic synovial inflammation, abnormal angiogenesis, and fibrosis represent the critical pathologies in the glenohumeral capsule. However, no pharmacotherapy has been introduced to treat this pathology. Tetrandrine (TET) has been proposed as a treatment for many diseases due to its strong anti-inflammatory, anti-angiogenic, and anti-fibrotic effects. PURPOSE: To study the anti-inflammatory, anti-angiogenic, and anti-fibrotic effects of TET on FS, and identify whether TET can prevent the development of FS in rats. STUDY DESIGN: A controlled laboratory study. METHODS: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into control, TET, and FS groups. The TET group was intraperitoneally injected with TET every 2 days. TET and saline treatment were started on the day of FS surgery. After 8 weeks, the animals were sacrificed, and samples were collected for X-ray examination, glenohumeral range of motion (ROM) evaluation, histology and immunohistochemistry analysis, transmission electron microscopy (TEM) observation, and profibrogenic factors as well as proinflammatory cytokines measurements. RESULTS: No significant difference in shoulder ROM was observed between the TET and control groups, but a significant difference was noted between these groups and the FS group (P < 0.01). Immunohistochemical staining showed no abnormal angiogenesis or fibrosis in the TET group or the control group. However, significant angiogenesis, collagen remodeling, and fibrosis were observed in the FS group, and the expression and proportion of type I and type III collagen in the FS group were significantly higher than those in the TET group or the control group (P < 0.01). TEM observation showed that TET protected the ultrastructure of collagen fibrous reticular arrangement of the articular capsule and prevented the formation of scar-like fibrotic structures, which are unique to FS. The significantly increased expression of Smad7 and the suppressed expression of Smad 2 in the TET group compared with that of the FS group indicated that TET also significantly inhibited the TGF-ß1 intracellular signal pathway. The expression of profibrogenic factors and proinflammatory cytokines in the TET group and the control group was significantly lower than that in the TET group (P < 0.01). CONCLUSION: The results demonstrated that TET protected the normal reticular structure of the capsule during the freezing period and prevented the development of FS by inhibiting inflammation, angiogenesis, and fibrosis in a rat FS model. CLINICAL RELEVANCE: TET may be a safe and effective clinical medication for preventing and treating FS.

Macrophage migration inhibitory factor regulates joint capsule fibrosis by promoting TGF-ß1 production in fibroblasts.

Joint capsule fibrosis caused by excessive inflammation results in post-traumatic joint contracture (PTJC). Transforming growth factor (TGF)-ß1 plays a key role in PTJC by regulating fibroblast functions, however, cytokine-induced TGF-ß1 expression in specific cell types remains poorly characterized. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology. In this study, we investigated whether MIF can facilitate TGF-ß1 production from fibroblasts and regulate joint capsule fibrosis following PTJC. Our data demonstrated that MIF and TGF-ß1 significantly increased in fibroblasts of injured rat posterior joint capsules. Treatment the lesion sites with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP) reduced TGF-ß1 production and relieved joint capsule inflammation and fibrosis. In vitro, MIF facilitated TGF-ß1 expression in primary joint capsule fibroblasts by activating mitogen-activated protein kinase (MAPK) (P38, ERK) signaling through coupling with membrane surface receptor CD74, which in turn affected fibroblast functions and promoted MIF production. Our results reveal a novel function of trauma-induced MIF in the occurrence and development of joint capsule fibrosis. Further investigation of the underlying mechanism may provide potential therapeutic targets for PTJC.

Why Does Hip Arthroscopy Fail? Indications and PEARLS for Revision Success.

The surgical treatment of femoroacetabular impingement has been shown to have successful early and mid-term clinical outcomes. Despite these favorable clinical outcomes that have been published in the literature, there is a subgroup of patients that present with continued or recurrent symptoms after surgical treatment. Not only has there been an increase in the number of hip arthroscopy procedures, but also there has been a corresponding increase in the number of revision hip arthroscopy and hip preservation surgeries. Previous studies have reported residual deformity to be the most common reason for revision hip arthroscopy. However, chondral, labral, and capsular considerations also are important when addressing patients not only in the primary but also, the revision setting. In this review, we outline the evaluation and treatment of the patient that presents with continued hip and groin pain after undergoing a hip.

Formation process of joint contracture after anterior cruciate ligament reconstruction in rats.

Knee joint contracture is often induced by anterior cruciate ligament reconstruction (ACLR). However, the temporal and spatial arthrofibrotic changes following inflammatory events, which occur in parallel with the formation of joint contractures after ACLR, are unknown. This study aimed to reveal: (a) time-dependent changes in myogenic and arthrogenic contractures; and (b) the process of arthrofibrosis development after ACLR. ACLR was performed on knees of rats unilaterally. Passive ranges of motions (ROMs) before and after myotomy, as well as inflammatory and fibrotic reactions, were examined before and after the surgery at various periods up to 56 days. Both ROMs before and after myotomy exhibited their lowest value on day 7 and increased thereafter in a time-dependent manner; nevertheless, significant restrictions remained by day 56. Myotomy partially increased ROMs at all time points, indicating contribution of the myogenic component to ACLR-induced contracture. Inflammatory and fibrotic reactions peaked on day 7. Arthrofibrosis, characterized by the thickening of the joint capsule and the shortening of the synovial length, was established by day 7 and was not completely resolved by day 56. Our results indicate that: (a) both myogenic and arthrogenic contractures generated through ACLR develop maximally by day 7 after surgery and subside thereafter, but persist at least until day 56; and (b) arthrofibrosis is established by day 7 after surgery and is not completely resolved by day 56. These findings suggest that treatment and intervention for preventing joint contracture after ACLR should be performed within the first 7 days after surgery.

Increased levels of inflammatory markers in the subscapularis tendon and joint capsule in patients with subacromial impingement.

PURPOSE: To analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with subacromial impingement syndrome and compare them with samples from male patients with post-traumatic recurrent shoulder instability, to detect increased inflammatory activity that might be present inside the humeroscapular joint. METHODS: Twenty male patients scheduled for surgery for either subacromial decompression or Bankart reconstruction were included. Four biopsies from each patient were obtained during surgery from the capsule and the subscapularis tendon. Each specimen was analyzed for TNF-α, IL-6, CD-3 and CD-72. Multiplex fluorescence immunohistochemistry was performed on histological samples from the capsule and tendon to demonstrate the level of inflammatory markers. Fluorescence microscope images were acquired using an automated scanning system. On each slide, the number of pixels was registered and used in the analyses. RESULTS: The subacromial impingement syndrome group comprised eight patients, median age 53 (45-74) years, while the instability group 12, median age 27 (22-48) years (p < 0.00001). The amount of IL-6 and TNF-α was significantly higher in the subscapularis tendon of the patients with subacromial impingement syndrome compared with instability patients (p = 0.0015 and p = 0.0008 respectively). In the capsular samples, significantly higher amount of TNF-α and CD-72 was found in patients with subacromial impingement syndrome compared with instability patients (p < 0.0001 for both). On the other hand, the amount of CD-3 was significantly higher in the instability group (p = 0.0013). CONCLUSIONS: This study provides evidence that an extended inflammatory process is present, not only in the subacromial bursa but also in the glenohumeral joint in patients with subacromial impingement syndrome. LEVEL OF EVIDENCE: Level III. CLINICAL RELEVANCE: To develop a treatment targeted towards intra-articular inflammatory cytokines appears appealing.

Increased posterior shoulder capsule thickness in youth elite handball players: a sonographic investigation.

PURPOSE: Range of motion adaptations in the shoulders of overhead throwing athletes have been reported, but knowledge about the development of soft-tissue adaptations is limited. The purpose of this study was to investigate differences in posterior shoulder capsule thickness and internal rotation between the throwing and non-throwing shoulder. METHODS: On the basis of the sample size calculation, we assessed 63 youth elite handball players (33 boys and 30 girls, mean age: 13.6 ± 0.9 years) for glenohumeral internal and external rotational range of motion, humeral retrotorsion, and posterior capsule thickness (PCT) with a manual goniometer and a portable ultrasound device and calculated sports-specific differences between the throwing and non-throwing shoulder as well as correlations with PCT. RESULTS: Youth handball players showed side-to-side differences in internal rotation, external rotation, and humeral retrotorsion between the throwing and non-throwing shoulder. Posterior shoulder capsules were 1.21 times thicker (95% confidence interval: 1.1-1.3) in the throwing shoulder than in the non-throwing shoulder (1.3 ± 0.3 mm vs. 1.2 ± 0.2 mm, P < .0001). Loss of internal rotation did not correlate with PCT. CONCLUSIONS: In youth elite handball athletes, posterior shoulder tightness and subsequent sports-specific loss of internal rotation in the throwing shoulder are not related to PCT. Thus, in this age class, other (soft-tissue) factors must be responsible for this condition.

Rheumatoid arthritis-associated bone erosions: evolving insights and promising therapeutic strategies.

The human immune system has evolved to recognize and eradicate pathogens, a process that is known as "host defense". If, however, the immune system does not work properly, it can mistakenly attack the body's own tissues and induce autoimmune diseases. Rheumatoid arthritis (RA) is such an autoimmune disease in which the synovial joints are predominately attacked by the immune system. Moreover, RA is associated with bone destruction and joint deformity. Although biologic agents have propelled RA treatment forward dramatically over the past 30 years, a considerable number of patients with RA still experience progressive bone damage and joint disability. That is to be expected since current RA therapies are all intended to halt inflammation but not to alleviate bone destruction. A better understanding of bone erosions is crucial to developing a novel strategy to treat RA-associated erosions. This review provides insights into RA-associated bone destruction and perspectives for future clinical interventions.

Lumican promotes joint fibrosis through TGF-ß signaling.

Joint contracture (also known as arthrofibrosis) is a fibrotic joint disorder characterized by excessive collagen production to form fibrotic scar tissue and adhesions within joint capsules. This can severely affect day-to-day activities and quality of life because of a restricted range of motion in affected joints. The precise pathogenic mechanism underlying joint contractures is not fully understood. Lumican belongs to the class II small leucine-rich repeat proteoglycan superfamily, which makes up collagen fibrils in the extracellular matrix. Lumican is ubiquitously expressed in the skin, liver, heart, uterus and articular cartilage and has reported roles in cell migration, proliferation, angiogenesis and Toll-like receptor 4 signaling. Previous research has suggested that lumican is involved in the pathogenesis of several fibrotic diseases. Because joint contracture resembles a fibrotic disease, we aimed to investigate the role of lumican in the development of joint contracture in vitro. Here, we showed that protein levels were up-regulated in the fibrotic joint capsule versus control. We observed that lumican significantly enhanced the proliferation, migration and fibroblast-myofibroblast transition of synovial fibroblasts. Moreover, lumican led to increased transcription of alpha-smooth muscle actin, matrix metallopeptidase 9, Collagen I, plasminogen activator inhibitor 1 and transforming growth factor-ß in vitro. Lumican treatment promoted collagen lattice contraction in a dose-dependent manner as early as 24 h after treatment. Thus, our studies reveal that lumican could promote fibroblast-myofibroblast transition and joint contracture.

There is a correlation between histopathological findings of joint capsule and synovium, and postoperative clinical outcomes and treatment in patients with isolated type II superior labrum anterior posterior lesions.

OBJECTIVES: This study aims to histologically examine the joint capsule and synovium to determine the correlation between histopathological findings and postoperative clinical outcomes in patients with isolated type II superior labrum anterior posterior (SLAP) lesions. PATIENTS AND METHODS: Thirty-eight patients (24 males, 14 females; mean age 53.2±6.6 years; range, 45 to 67 years) who underwent arthroscopic treatment of type II SLAP lesions between June 2017 and September 2018 were evaluated prospectively. Visual analog scale (VAS), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) scores of all patients were recorded preoperatively, and at 6th and 12th months postoperatively. Biceps tenotomy was applied as arthroscopic surgical treatment in all patients. Biopsy materials obtained from rotator interval joint capsule and synovium during the arthroscopy were evaluated histopathologically. The density of the vessels in the specimens was defined as low, medium, and high by the pathologist. The patients with medium or low vessel density in specimens were group 1 (n=14) and those with high vessel density group 2 (n=24). RESULTS: In group 2, preoperative VAS score was significantly higher. There was no difference between the scores of the groups except for the sixth month SST score which was significantly higher in group 1. Histopathological evaluation revealed that the number of lymphocytes, fibroblasts, mast cells, myofibroblast, synovial lining cells, macrophages, and amount of collagen in connective tissue were significantly higher in group 2. In five patients of group 2, the rehabilitation program was interrupted due to pain and difficulty in gaining a range of motion during the first four weeks postoperatively. Four of these patients recovered with medication and long-duration physiotherapy. Shoulder stiffness developed in one patient who required arthroscopic release and further rehabilitation. CONCLUSION: There is a correlation between histopathological findings of joint capsule and synovium, and postoperative clinical outcomes and treatment in patients with isolated type II SLAP lesions. Almost 20% of patients who had pathologic histological findings in joint capsule and synovium needed pain control and long-duration rehabilitation program after arthroscopic surgery for better shoulder function recovery and prevention of shoulder stiffness.

The human arthritic hip joint is a source of mesenchymal stromal cells (MSCs) with extensive multipotent differentiation potential.

BACKGROUND: While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint. METHODS: MSCs were isolated and multiplied in adherent monolayer cell cultures. Osteogenesis and adipogenesis were induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ß1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes. RESULTS: This in vitro research showed that the isolated cells from all four donor tissues grew plastic-adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MSC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MSC-pellets, except for those from the LCF. Interestingly, all differentiated MSCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition, the examination of an exemplary selected donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis. CONCLUSIONS: This study proved the presence of MSC-like cells in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MSCs used. Further research is necessary to fully determine the tripotent differentiation potential of cells isolated from the LCF and capsule tissue of the hip joint.

Histopathological Evaluation of Mechanoreceptors in the Metatarsophalangeal Joint Capsule in Hallux Valgus.

To date, we could find no study concerning the relationship between mechanoreceptors in the joint capsule of the first metatarsophalangeal joint and hallux valgus deformity. We aimed to investigate the presence of mechanoreceptors in samples obtained from the first metatarsophalangeal joint capsules of patients with hallux valgus deformity to improve our understanding of the clinical and histopathological features of the disease. Samples were taken from the first metatarsophalangeal joint capsules of 13 fresh-frozen cadavers with normal anatomy (controls) and 29 patients undergoing surgery for hallux valgus (cases). For light microscopy, excised specimens were fixed in 10% formaldehyde and processed for routine histopathological investigation. All samples were dehydrated in a series of ethanol, cleared in xylene, and embedded in paraffin. Orientation of collagen fibers was determined on Masson's trichrome-stained sections, and mechanoreceptors were evaluated on S-100-immunostained sections. In the sections stained with Masson's trichrome, the orientation of collagen fibers was regular in the control group. However, coarse and disoriented collagen bundles were observed in the hallux valgus cases (P ≤ .05). S-100 immunostaining was positive in the sections of both the cases and controls. Finally, free nerve endings were more abundant in the samples obtained from the capsules of hallux valgus cases than from the control group (P ≤ .05). An increase in the number of free nerve endings within the capsules of the first metatarsophalangeal joints in feet with hallux valgus deformity might have a role in the development of clinically relevant joint pain and instability.

Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization.

This study aimed to develop a rabbit model of knee contracture in extension and investigate the natural history of motion loss and time-dependent changes in the joint capsule after immobilization. We immobilized the unilateral knee joints of 32 rabbits by maintaining the knee joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of joint contracture by measuring the joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor ß1 (TGF-ß1) in the anterior and posterior joint capsules. After 2 weeks of joint immobilization, the knee joint range of motion was limited, the synovial membrane of the suprapatellar and posterior joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-ß1 were elevated in the anterior and posterior joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior joint capsules after joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-ß1 may be related to joint capsule fibrosis and may be one of the causes of joint contracture.

Biomarkers associated with idiopathic frozen shoulder: a systematic review.

Background: The pathophysiology of idiopathic frozen shoulder (FS) remains poorly described. There is a lack of differentiation between idiopathic and secondary cause. The aim of this systematic review was to summarize the evidence regarding the pathophysiology of idiopathic FS on a molecular level and emphasize the clinical relevance. Methods: A database search of Medline, EMBASE and Cochrane Central Register of Controlled Trials from inception to April 2018 was performed. Participants who underwent previous injections or surgeries were excluded. A thorough selection and quality assessment process using the Cochrane Risk of Bias assessment tool and the Joanna Briggs Institute Critical Appraisal Checklist was conducted by two reviewers independently. Results: A total of 15 studies analyzing 333 study subjects were included. Twelve studies evaluated capsular tissue and three studies investigated blood samples. The tissue samples revealed increased expression of various inflammatory cytokines including interleukins, cyclooxygenase and tumor necrosis factor. Several types of acid-sensing ion channels (ASIC1 and ASIC3) were associated with disturbed neurogenesis and melatonin-regulated pain mechanism. The blood samples showed prevalence of specific interleukin and metalloproteinase genotypes. A decreased matrix metalloproteinase/tissue inhibitor of metalloproteinase ratio was found both in tissue and blood. Conclusion: The findings indicate an abnormal local neurogenesis with possible regulation through melatonin. The disturbance in remodeling of the extracellular matrix and in collagen translation, together with a persistent inflammation and an impaired healing, all interact in the process that leads to persistent fibrosis. There is global fibroplasia with localized anterior capsule contracture.