The footprint of the anterior horn of medial meniscus: A novel and reliable landmark for the tibial vertical cut in Oxford mobile-bearing medial unicompartmental knee arthroplasty.

BACKGROUND: Tibial vertical cut is crucial for rotational position and bony coverage in Oxford mobile-bearing medial unicompartmental knee arthroplasty (UKA). This study aimed to determine whether the footprint of the anterior horn of medial meniscus (FAM) is a reliable landmark for tibial vertical cut. METHODS: The FAM and the line through FAM and the edge of anterior cruciate ligament insertion (FAMA line) were identified by dissection five knee joint specimens. The angle between FAMA line and standard Akagi's line was measured. From 2022 to 2023, 64 patients (74 knees) diagnosed as anteromedial osteoarthritis were included to undergo primary Oxford medial UKA by two surgeons (Group 1 and 2), using FAMA line as a landmark for tibial vertical cut. The anteroposterior (AP) length, mediolateral (ML) length of tibial cut and tibial prothesis were measured by vernier caliper. ML/AP ratio was also calculated, and data were compared intragroup and intergroup. Mediolateral position and external rotation of tibial components were assessed postoperatively. RESULTS: FAMA line was parallel to standard Akagi's line. No significant differences were found in AP and ML lengths between tibial cut and tibial component (AP different value = 0.007 ± 0.154 cm, P = 0.674, ML different value = 0.020 ± 0.195 cm, P = 0.155). The ML/AP ratio was similar between the two groups (P = 0.141, 0.646, 0.255, 0.607, 0.384, size AA âˆ¼ D). No significant difference was found in mediolateral position (0.87 ± 0.03 vs. 0.86 ± 0.03, P = 0.156) and external rotation (6.88 ± 2.08 vs. 6.68 ± 2.22, P = 0.746) of the tibial component between the two groups. CONCLUSION: The FAM is a reliable landmark for tibial vertical cut in Oxford UKA.

Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders.

Triggering receptor expressed on myeloid cell 2 (TREM2) signaling often drives opposing effects in traumatic versus demyelinating CNS disorders. Here, we identify two distinct phenotypes of microglia and infiltrating myeloid populations dependent on TREM2 expression levels at the acute stage and elucidate how they mediate the opposing effects of TREM2 in spinal cord injury (SCI) versus multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High TREM2 levels sustain phagocytic microglia and infiltrating macrophages after SCI. In contrast, moderate TREM2 levels sustain immunomodulatory microglia and infiltrating monocytes in EAE. TREM2-ablated microglia (purine-sensing phenotype in SCI and reduced immunomodulatory phenotype in EAE) drive transient protection at the acute stage of both disorders, whereas reduced phagocytic macrophages and lysosome-activated monocytes lead to contrasting neuroprotective and demyelinating effects in SCI versus EAE, respectively. Our study provides comprehensive insights into the complex roles of TREM2 in myeloid populations across diverse CNS disorders, which has crucial implications in devising TREM2-targeting therapeutics.

Poly-l-lactide-co-ε-caprolactone (PLCL) and poly-l-lactic acid (PLLA)/gelatin electrospun subacromial spacer improves extracellular matrix (ECM) deposition for the potential treatment of irreparable rotator cuff tears.

Biodegradable subacromial spacer implantation has become practicable for the treatment of irreparable rotator cuff tears (IRCT). However, the relative high degradation rate and inferior tissue regeneration properties of current subacromial spacer may lead to failure regards to long-term survival. It is reported that satisfactory clinical results lie in the surrounding extracellular matrix (ECM) deposition after implantation. This study aims to develop a biological subacromial spacer that would enhance tissue regeneration properties and results in better ECM deposition. Physicochemical properties were characterized on both poly-l-lactide-co-ε-caprolactone (PLCL) dip-coating spacer (monolayer spacer, MS) and PLCL dip-coating + Poly-l-Lactic Acid (PLLA)/Gelatin electrospun spacer (Bilayer Spacer, BS). Cytocompatibility, angiogenesis, and collagen inducibility were evaluated with tendon fibroblasts and endothelial cells. Ultrasonography and histomorphology were used to analyze biodegradability and surrounding ECM deposition after the implantation in vivo. BS was successfully fabricated with the dip-coating and electrospinning technique, based on the human humeral head data. In vitro studies demonstrated that BS showed a greater cytocompatibility, and increased secretion of ECM proteins comparing to MS. In vivo studies indicated that BS promoted ECM deposition and angiogenesis in the surrounding tissue. Our research highlights that BS exhibits better ECM deposition and reveals a potential candidate for the treatment of IRCT in future.

Exosomal long non-coding RNA TRAFD1-4:1 derived from fibroblast-like synoviocytes suppresses chondrocyte proliferation and migration by degrading cartilage extracellular matrix in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, autoimmune and systemic inflammatory disease affecting 1% of the population worldwide. Immune suppression of the activity and progress of RA is vital to reduce the disability and mortality rate as well as improve the quality of life of RA patients. However, the immune molecular mechanism of RA has not been clarified yet. Our results indicated that exosomes derived from TNFα-stimulated RA fibroblast-like synoviocytes (RA-FLSs) suppressed chondrocyte proliferation and migration through modulating cartilage extracellular matrix (CECM) determining by MTS assay, cell cycle analysis, Transwell assay and Western blot (WB). Besides, RNA sequencing and verification by qRT-PCR revealed that exosomal long non-coding RNA (lncRNA) tumor necrosis factor-associated factor 1 (TRAF1)-4:1 derived from RA-FLSs treated with TNFα was a candidate lncRNA, which also inhibited chondrocyte proliferation and migration through degrading CECM. Moreover, RNA sequencing and bioinformatics analysis identified that C-X-C motif chemokine ligand 1 (CXCL1) was a target mRNA of miR-27a-3p while miR-27a-3p was a target miRNA of lnc-TRAF1-4:1 in chondrocytes. Mechanistically, lnc-TRAF1-4:1 upregulated CXCL1 expression through sponging miR-27a-3p as a competing endogenous RNA (ceRNA) in chondrocytes identifying by Dual-luciferase reporter gene assay. Summarily, exosomal lncRNA TRAFD1-4:1 derived from RA-FLSs suppressed chondrocyte proliferation and migration through degrading CECM by upregulating CXCL1 as a sponge of miR-27a-3p. This study uncovered a novel RA-related lncRNA and investigated the roles of RA-FLS-derived exosomes and exosomal lnc-TRAF1-4:1 in articular cartilage impairment, which might provide novel therapeutic targets for RA.

Effects of integrated bioceramic and uniaxial drawing on mechanically-enhanced fibrogenesis for bionic periosteum engineering.

Periosteum is clinically required for the management of large bone defects. Attempts to exploit the periosteum's participation in bone healing, however, have rarely featured biological and mechanical complexity for the scaffolds relevant to translational medicine. In this regard, we report engineering of bioinspired periosteum with co-delivery of ionic and geometry cues. The scaffold demonstrated microsheet-like fibre morphology and was developed based on bioresorbable poly(-caprolactone) and bioactive copper-doped tricalcium phosphate (Cu-TCP). A coordinated interaction was found between the effects of Cu-TCP addition and uniaxial drawing, leading to tunable fibrogenesis for different fibre morphologies, organisation, and surface wettability. The coordination resulted in significant enhancements in Young's Modulus, yield stress and ultimate stress along fibrous alignment, without causing reductions across fibres. This demonstrated mechanical anisotropy of the scaffold similar to natural periosteum, and seeding with mouse calvarial preosteoblasts, the scaffold supported cell alignment with deposition of CaP-like nodules and extracellular matrix. This work provides new insights on periosteum engineering with osteo-related composite fibres. The artificial periosteum can be used in clinical settings to facilitate repair of large bone defects.

The Regenerative Role of Gelatin in PLLA Electrospun Membranes for the Treatment of Chronic Massive Rotator Cuff Injuries.

Failing to regenerate native tendon tissue in chronic massive rotator cuff tears (CMRCTs) results in high retear rates after surgery. Gelatin is a hydrolyzed form of collagen which is bioactive and biocompatible. This study intends to investigate the suitability of integrating gelatin to poly (l-lactic acid) (PLLA) fibrous membranes for promoting the healing of CMRCTs. PLLA/Gelatin electrospun membranes (PGEM) are fabricated using electrospinning technology. The fourier transform infrared, static contact angles are tested sequentially. Cytocompatibility is evaluated with rat tendon fibroblasts and human umbilical endothelial cells (HUEVCs) lines. CMRCTs rat models are established and assigned into three groups (the sham group, the repaired group, and the augmentation group) to perform histomorphological and biomechanical evaluations. Gelatin is successfully integrated into PLLA fibrous membranes by the electrospinning technique. In vitro studies indicate that PGEM shows a great cytocompatibility for rat tendon fibroblasts and HUEVCs. In vivo studies find that applications of PGEM significantly promote well-aligned collagen I fibers formation and enhance biomechanical properties of the repaired tendon in CMRCTs rat models. In summary, gelatin promotes tendon fibroblasts and HUEVCs adhesion, migration, and proliferation on the PLLA fibrous membranes, and PGEM may provide a great prospect for clinical application.

Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway.

Mesenchymal stem cells (MSCs) have been described to induce angiogenesis in various tissues and have been used for the development of novel cell-based therapies. Increasing evidence suggests that MSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions. However, the mechanisms by which MSC-derived exosomes secreted under hypoxia enhance angiogenesis still remain unclear. To study exosome physiology under hypoxic or normoxic conditions, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs). Furthermore, we detected the uptake of exosomes by human umbilical vein endothelial cells (HUVECs) by immunofluorescence staining. In addition, we determined the effects of exosomes on cell viability, migration and tube formation in HUVECs by Cell Counting Kit-8, migration and tube formation assays, respectively. We examined the expression of key proteins related to exosome-induced angiogenesis by BMSCs cultured under hypoxic conditions by western blot. Exosomes released by BMSCs cultured under hypoxic conditions enhanced cell proliferation, migration and angiogenesis of HUVECs. Hypoxia induced the expression of high mobility group box 1 protein (HMGB1) in BMSC-derived exosomes, and silencing of HMGB1 abolished the angiogenic effect in HUVECs. Furthermore, exosomal HMGB1 activated the JNK signaling pathway and induced hypoxia-inducible factor-1α/vascular endothelial growth factor expression, consequently enhancing angiogenesis in HUVECs. Our data reveal that exosomal HMGB1 promotes angiogenesis via JNK/hypoxia-inducible factor-1α signaling. Therefore, BMSC exosomes derived under hypoxia may have potential for development of novel treatment strategies for angiogenesis-related diseases.

Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma.

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

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.

Anti-osteosarcoma property of decorin-modified titanium surface: A novel strategy to inhibit oncogenic potential of osteosarcoma cells.

Osteosarcoma is the most common bone sarcoma in adolescents. Decorin (DCN) has been proposed to be a new anti-osteosarcoma therapeutic strategy. Our previous study has loaded decorin on titanium (Ti) surface by polydopamine (DOPA) as an anchor to enhance osseointegration. In this study, we investigated the effect of decorin-coated Ti substrates (TI-DOPA-DCN) on the oncogenic potential of osteosarcoma cells SAOS-2. The substrates were placed in 24-well plates for cell culture. Cell viability was determined by Cell Counting Kit-8 (CCK8) assay. Apoptosis was evaluated by DAPI staining and Annexin V-FITC/PI double staining analysis. Cell cycle was analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. For co-culture, the pre-osteogenic cells MEC3T3-E1 and osteosarcoma cells SAOS-2 were stained with cell membrane fluorescent dyes, and then mixed (1:1) for co-culture. The cells were observed under a fluorescence microscope at four time points of 24, 48, 72, and 96 h. The results showed that TI-DOPA-DCN substrate can selectively inhibit cell proliferation of osteosarcoma cells but not pre-osteoblasts. However, the cell cycle of SAOS-2 was not affected by TI-DOPA-DCN substrates. Both DAPI staining and Annexin V-FITC/PI double staining analysis revealed that TI-DOPA-DCN substrates induced apoptosis of osteosarcoma cells. Transwell assay showed that TI-DOPA-DCN substrates inhibited invasion and migration of osteosarcoma cells. Moreover, TI-DOPA-DCN substrates inhibited the growth of osteosarcoma cells but promoted that of pre-osteoblasts in the coculture system. Taken together, these findings suggested that decorin coating on Ti surface simultaneously inhibited the oncogenic potential of osteosarcoma cells but enhanced cell growth of pre-osteoblasts, which could be applied to surface modification of Ti orthopedic implant.

A risk signature-based on metastasis-associated genes to predict survival of patients with osteosarcoma.

Osteosarcoma (OS) is the most common primary solid malignant bone tumor, and its metastasis is a prominent cause of high mortality in patients. In this study, a prognosis risk signature was constructed based on metastasis-associated genes. Four microarrays datasets with clinical information were downloaded from Gene Expression Omnibus, and 256 metastasis-associated genes were identified by limma package. Further, a protein-protein interaction network was constructed, and survival analysis was performed using data from the Therapeutically Applicable Research to Generate Effective Treatments data matrix, identifying 19 genes correlated with prognosis. Six genes were selected by the least absolute shrinkage and selection operator regression for multivariate cox analysis. Finally, a three-gene (MYC, CPE, and LY86) risk signature was constructed, and datasets GSE21257 and GSE16091 were used to validate the prediction efficiency of the signature. The survival times of low- and high-risk groups were significantly different in the training set and validation set. Additionally, gene set enrichment analysis revealed that the genes in the signature may affect the cell cycle, gap junctions, and interleukin-6 production. Therefore, the three-gene survival risk signature could potentially predict the prognosis of patients with OS. Further, proteins encoded by CPE and LY86 may provide novel insights into the prediction of OS prognosis and therapeutic targets.

Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation.

Joint contracture is a fibrotic complication induced by joint immobilization and trauma, which is characterized as excessive myofibroblast proliferation in joint capsule. The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction. Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro, but the major challenge is the low aqueous solubility and biological activity of curcumin. In this study, hyaluronic acid-curcumin (HA-Cur) conjugate was synthesized to suppress myofibroblasts in joint contracture. Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-ß (TGF-ß). The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (PCR), methylation-specific PCR, western blot, transwell migration assay and proliferation assay. Results showed that 30 µM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2 (PTGER2) and inhibiting TGF-ß signaling. This may provide a mechanism for the treatment of joint contracture, and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.

Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model.

OBJECTIVE: Autograft microskin transplantation has been widely used as a skin graft therapy in full-thickness skin defect. However, skin grafting failure can lead to a pathological delay wound healing due to a poor vascularization bed. Considering the active role of adipose-derived stem cell (ADSC) in promoting angiogenesis, we intend to investigate the efficacy of autograft microskin combined with ADSC transplantation for facilitating wound healing in a full-thickness skin defect mouse model. MATERIAL AND METHODS: An in vivo full-thickness skin defect mouse model was used to evaluate the contribution of transplantation microskin and ADSC in wound healing. The angiogenesis was detected by immunohistochemistry staining. In vitro paracrine signaling pathway was evaluated by protein array and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. RESULTS: Co-transplantation of microskin and ADSC potentiated the wound healing with better epithelization, smaller scar thickness, and higher angiogenesis (CD31) in the subcutaneous layer. We found both EGF and VEGF cytokines were secreted by microskin in vitro. Additionally, secretome proteomic analysis in a co-culture system of microskin and ADSC revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2, which most likely supported the angiogenesis effect as observed. CONCLUSION: Overall, we concluded that the use of ADSC partially modulates microskin function and enhances wound healing by promoting angiogenesis in a full-thickness skin defect mouse model.

Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule.

Joint contracture is increasingly regarded as a clinical problem that leads to irreversible dysfunction of the joint. It is a pathophysiological process following joint injury, which is marked by the activation of myofibroblasts. There is currently no effective treatment for the prevention of joint contracture. Curcumin is a polyphenol pigment extracted from turmeric, which possesses anti-inflammatory, antioxidative, and antitumor properties. In the present study, we demonstrated that curcumin exerts a protective effect against joint contracture via the inhibition of myofibroblast proliferation and migration in a time- and concentration-dependent manner. Moreover, we indicated that phosphatase and tension homolog (PTEN) was downregulated in myofibroblasts in vitro and in the contracture capsule tissues of patients in vivo. Additionally, western blot analysis revealed a negative correlation between the expression levels of PTEN and the fibrosis marker protein alpha smooth muscle cell actin. Methylation-specific PCR results suggested that curcumin was able to demethylate PTEN in a similar manner to the demethylation agent 5-azacytidine, increasing PTEN expression and further inhibiting phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling. In conclusion, our data illustrate part of the mechanism of curcumin inhibition in joint contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of joint contracture.

Overexpression of chaperonin containing T-complex polypeptide subunit zeta 2 (CCT6b) suppresses the functions of active fibroblasts in a rat model of joint contracture.

BACKGROUND: Joint contracture is a fibrous disease characterized as joint capsule fibrosis that results in joint dysfunction and disability. The purpose of this study was to analyze the biological activities of chaperonin containing T-complex polypeptide (CCT) subunits and to determine the role of CCT chaperone in joint contracture in a rat model. METHODS: In this study, the rat model of joint contracture was established by immobilizing the rat knee for 8 weeks. Then, fibroblasts were isolated from the posterior joint capsule and were cultured for functional analysis such as qRT-PCR, Western blot, transwell assay, and collagen assay. The effect of CCT subunit was determined by employing a lentivirus containing target gene and transfecting it into fibroblasts. RESULTS: Results of qRT-PCR and Western blot showed that among all CCT subunits, CCT6b significantly decreased in the fibroblasts from contractive joints compared to cells from normal joints (p < 0.05). Overexpression of CCT6b by transfection of lentivirus containing CCT6b gene to active fibroblasts significantly inhibited fibrous marker (α-SMA, COL-1) expressions, fibroblast migration, and collagen synthesis (all p < 0.05). Moreover, fibrosis-related chaperone CCT7 expression was decreased with CCT6b overexpression (p < 0.05). CONCLUSION: The biological activities of CCT subunits in fibroblasts from the joint contracture rat model were analyzed in this study. CCT6b significantly decreased in the active fibroblasts, and overexpression of CCT6b significantly inhibited fibroblast functions. These findings indicate that CCT6b appears to be a potential molecular biomarker and therapeutic target for the novel therapies of joint contracture.

Arthroscopic partial capsulotomy for exposure and treatment of hip disease.

Hip arthroscopy is an effective method for the diagnosis and treatment of hip joint pathologies. However, gaining access to the central and peripheral compartments is challenging. The present study aimed to assess the advantages of using an arthroscopic extra-capsular approach and partial capsulotomy for access and subsequent management of hip diseases. Patients subjected to hip arthroscopy by partial capsulotomy for exposure and treatment of hip diseases between February 2012 and February 2016 were retrospectively analyzed. A total of 32 patients, including 19 males and 13 females, aged 19-48 years (median age, 36 years), had undergone the procedure. Firstly, the distal anterior lateral and anterolateral arthroscopic approach with blunt dissection was performed. Subsequently, a T-shaped partial capsulotomy was established to achieve adequate exposure. The shaver, radiofrequency probe and tissue penetrating suture grasper were then inserted to perform procedures including debridement of the synovium, suturing of the glenoid labrum. During surgery, a probe hook was used to push the capsule section limbs or pull the sutures placed on the capsule section limbs to improve exposure. For patients with pre-operative anterior instability, ligamentous laxity or acetabular dysplasia capsules were sutured to finish capsule closure. The pre-operative and post-operative Visual Analogue Scale (VAS) score and modified Harris hip score (MHHS) were used to assess the effectiveness of the procedure. No obvious post-operative complications were encountered. The mean follow-up time was 22.4 months (range, 18-32 months) and 31 patients completed the follow-up, while 1 patient was lost to follow-up. Compared with the pre-operative score, the MHHS was significantly increased (66.2±6.0 vs. 82.6±5.2; P<0.05) and the VAS score was significantly decreased (6.5±1.1 vs. 1.2±0.7; P<0.05) at the end of the follow-up. In conclusion, arthroscopic partial capsulotomy provides access to the peripheral and central compartments of the hip and is a relatively simple technique that is easy to master for surgeons with limited experience in hip surgery.

Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee joint contracture model.

Joint contracture is a common complication for people with joint immobility that involves fibrosis structural alteration in the joint capsule. Considering that endoplasmic reticulum (ER) stress plays a prominent role in the promotion of tissue fibrosis, we investigated whether the unfolded protein response (UPR) contributes to the fibrotic development in immobilization-induced knee joint contractures. Using a non-traumatic rat knee joint contracture model, twelve female Sprague-Dawley rats received knee joint immobilization for a period of 8 weeks. We found that fibrosis protein markers (type I collagen, α-SMA) and UPR (GRP78, ATF6α, XBP1s) markers were parallelly upregulated in rat primary cultured synovial myofibroblasts. In the same cell types, pre-treatment with an ER stress inhibitor, 4-phenylbutyric acid (4-PBA), not only abrogated cytokine TGFß1 stimulation but also reduced the protein level of UPR. Additionally, high reactive oxygen species (ROS) generation was detected in synovial myofibroblasts through flow cytometry, as expected. Notably, TGFß1-induced UPR was significantly reduced through the inhibition of ROS with antioxidants. These data suggest that ER stress act as a pro-fibrotic stimulus through the overexpression of ROS in synovial fibroblasts. Interestingly, immunohistochemical results showed an increase in the UPR protein levels both in human acquired joint contractures capsule tissue and in animal knee joint contracture tissue. Together, our findings suggest that ER stress contributes to synovial myofibroblastic differentiation in joint capsule fibrosis and may also serve as a potential therapeutic target in joint contractures.

Decreased fibrous encapsulation and enhanced osseointegration in vitro by decorin-modified titanium surface.

Orthopedic implants, using materials such as titanium, are extensively used in clinical surgeries. Despite its popularity, titanium is still inadequate to reliable osseointegration due to aseptic loosing. Fibrous encapsulation on the titanium implant interface prevents osseointegration and leads to the loosing of orthopedic implant. In this study, decorin was loaded on titanium surface by polydopamine film to examine fibrous encapsulation inhibition and bone growth acceleration. The coating of decorin was evaluated by X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. Quantitative analysis showed increased decorin coating on titanium surface when decorin in the loading solution increases. To test the effect of decorin modification, fibroblast and osteoblast cultures were utilized in vitro. The results showed that the functions of fibroblasts (proliferation, migration and collagen synthesis) were significantly attenuated on the decorin-modified surfaces and this anti-fibrous effect could be due to fibrotic gene suppression by decorin. In contrast, osteoblastic activities, such as calcium deposition and alkaline phosphatase (ALP) activity, were enhanced by the modified decorin. These results suggest that decorin coating on titanium surface inhibited proliferation and function of fibroblasts and improved that of osteoblasts. Therefore, this study is potentially useful for enhancing orthopedic implant.

Chaperonin containing T-complex polypeptide subunit eta is a potential marker of joint contracture: an experimental study in the rat.

Joint contracture is a fibroproliferative disorder that restricts joint mobility, resulting in tissue degeneration and deformity. However, the etiology of joint contracture is still unknown. Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is reported to increase in fibrotic diseases. The purpose of this study was to investigate whether CCT-eta is implicated in joint contracture and to determine the role of CCT-eta in the progression of joint contracture by analyzing a rat model. We immobilized the left knee joint of rat by internal fixation for 8 weeks. The non-immobilized right leg served as a control. The range of motion (ROM) of the knee was investigated. Fibroblasts were obtained from the posterior joint capsule of the joints. The outcome was followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, fibroblast migration assay, and collagen assay. The effect of CCT-eta on the functions of fibroblasts was observed by utilizing a short inhibitory RNA (siRNA) targeting CCT-eta. The ROM of the immobilized joints was significantly limited compared to the contralateral joints (p < 0.05). Fibroblasts derived from the contractive joints showed higher mRNA and protein expressions of CCT-eta in parallel with alpha-smooth muscle actin (α-SMA) compared to the cells from the contralateral knees (p < 0.05). siRNA-mediated downregulation of CCT-eta inhibited the expressions of both CCT-eta and α-SMA. Moreover, the reduction of CCT-eta also significantly decreased fibroblast functions such as cell mobility and collagen synthesis (all p < 0.05). Our findings indicate that CCT-eta appears to be a potential marker of joint contracture disease.