Clinical outcomes of arthroscopic all-inside anterior talofibular ligament suture augmentation repair versus modified suture augmentation repair for chronic ankle instability patients.

BACKGROUND: To compare the clinical efficacies of arthroscopic anterior talofibular ligament suture augmentation repair and modified suture augmentation repair in patients with chronic ankle instability (CAI). METHODS: From October 2019 to August 2020, 100 patients with CAI were enrolled after propensity score matching analysis and observed for two years. Among them, 50 underwent modified suture augmentation repair and the other 50 underwent suture augmentation repair. The clinical efficacies of CAI treatments were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) clinical rating scale, visual analog scale (VAS), and anterior drawer test scores. RESULTS: The postoperative AOFAS score of the modified suture augmentation repair group (83.8 ± 11.3) was significantly higher than that of the suture augmentation repair group (76.3 ± 11.3; P = 0.001). The VAS (P = 0.863) and anterior drawer test (P = 0.617) scores were not significantly different between the two treatment groups. CONCLUSION: Both the modified suture augmentation repair and suture augmentation repair demonstrated good clinical efficacies. The AOFAS score of the modified suture augmentation repair group was superior to that of the conventional suture augmentation repair group. Thus, modified suture augmentation repair is a feasible and practical surgical technique for CAI treatment.

Trim21 Regulates the Postnatal Development and Thermogenesis of Brown Adipose Tissue.

Brown adipose tissue undergoes rapid postnatal development to mature and plays a crucial role in thermoregulation and energy expenditure, which protects against cold and obesity. Herein, it is shown that the expression of Trim21 mRNA level of interscapular brown adipose tissue elevates after birth, and peaks at P14 (postnatal day 14). Trim21 depletion severely impairs the maturation of interscapular brown adipose tissue, decreases the expression of a series of thermogenic genes, and reduces energy expenditure. Consistently, the loss of Trim21 also leads to a suppression of white adipose tissue "browning", in response to cold exposure and a ß-adrenergic agonist, CL316,243. In addition, Trim21-/- mice are more prone to high-fat diet-induced obesity compared with the control littermates. Taken together, the study for the first time reveals a critical role of Trim21 in regulating iBAT postnatal development and thermogenesis.

Novel biomimetic mesoporous silica nanoparticle system possessing targetability and immune synergy facilitates effective solid tumor immuno-chemotherapy.

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8+ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.

Biomechanical Study of Arthroscopic All-Inside Anterior Talofibular Ligament Suture Augmentation Repair, Plus Suture Augmentation Repair and Anterior Tibiofibular Ligament's Distal Fascicle Transfer Augmentation Repair.

Objective: To explore the biomechanical efficacy of arthroscopic all-inside anterior talofibular ligament (ATFL) suture augmentation repair, plus suture augmentation repair and anterior tibiofibular ligament-distal fascicle (ATiFL-DF) transfer augmentation repair, so as to provide a basis for the accurate selection of ATFL repair in clinical practice. Methods: Twenty-four (12 pairs) fresh frozen human cadaver ankle specimens were used. Six of the ankle specimens were set as the normal group, and the other 18 ankle specimens were used to establish ATFL injury models. The ATFL was then repaired using arthroscopic all-inside ATFL suture augmentation repair (suture augmentation group), plus suture augmentation repair (plus suture augmentation group) and ATiFL-DF transfer augmentation repair (biological augmentation group), respectively. After the repaired ATFL was separated, the ankle specimens were fixed on an electronic universal testing machine with a customized fixture for the tensile test, and the ultimate failure load (N) and stiffness (N/mm) of the ankle specimens were compared. Results: The ultimate failure load of the plus suture augmentation group (229.3 ± 66.7 N) was significantly higher than that in the normal group (148.2 ± 39.4 N, p = 0.045) and the biological augmentation group (131.3 ± 38.8 N, p = 0.013). There was no statistical difference in ultimate failure load between the suture augmentation group (167.2 ± 47.2 N), the normal group and the biological augmentation group. The stiffness of the plus suture augmentation group (26.2 ± 8.2 N/mm) was significantly higher than that in the normal group (12.1 ± 3.8 N/mm, p = 0.005) and the biological augmentation group (12.7 ± 5.2 N/mm, p = 0.007). The stiffness of the suture augmentation group (23.6 ± 7.0 N/mm) was significantly higher than that in the normal group (p = 0.024) and the biological augmentation group (p = 0.033). There was no statistical difference in stiffness between the plus suture augmentation group and the suture augmentation group, and no statistical difference in stiffness between the normal group and the biological augmentation group. Conclusions: The tensile strength and rigidity of plus suture augmentation repair were significantly better than those of normal ATFL, suture augmentation repair and ATiFL-DF transfer augmentation repair. Suture augmentation repair can obtain tensile strength similar to normal ATFL and ATiFL-DF transfer augmentation repair, and suture augmentation repair can obtain rigidity significantly better than normal ATFL and ATiFL-DF transfer augmentation repair. ATiFL-DF transfer augmentation repair can obtain tensile strength and rigidity similar to normal ATFL.

VEGFA-Enriched Exosomes from Tendon-Derived Stem Cells Facilitate Tenocyte Differentiation, Migration, and Transition to a Fibroblastic Phenotype.

Tendon-derived stem cells (TDSCs) play a vital role in repair of rotator cuff tear injuries by secreting paracrine proteins that regulate resident cell functions. Secreted exosomes may play a role in tendon injury repair by mediating intercellular communication; however, the detailed mechanisms by which TDSC-derived exosomes affect tenocyte development remain unknown. Here, we examined the effects of exosomes isolated from conditioned medium of TDSCs on tenocyte differentiation, migration, and transition to a fibroblastic phenotype in vitro. Successful isolation of exosomes from TDSCs was confirmed by high expression levels of CD81, CD63, CD9, and TSG101. Treatment with TDSC-derived exosomes promoted the growth and migration of cultured rat tenocytes, and increased the levels of the fibrosis markers collagen I, collagen III, scleraxis, tenascin C, and α-smooth muscle actin. Furthermore, vascular endothelial growth factor A (VEGFA) expression was higher in TDSC-derived exosomes than in TDSCs, and genetic knockdown of VEGFA suppressed the stimulatory effect of TDSC-derived exosomes on tenocyte development. Overall, these results demonstrate that VEGFA-enriched exosomes isolated from TDSCs promote differentiation and migration of cultured tenocytes and their transition to a fibroblastic phenotype. These data provide a new potential clinical treatment strategy for tendon injury.

Effects of 6-Hydroxykaempferol: A Potential Natural Product for Amelioration of Tendon Impairment.

Tendon impairment is a common injury associated with impairment of range of motion and pain. Currently, evidence has confirmed that natural herbs contribute to orthopedics and have shown excellent results in the clinical management of tendon impairment. Shujin Huoxue tablet (SHT) and its complex prescriptions are regularly used in tendon rupture therapy with positive results. This study aimed to discover the potential molecules that promote tendon healing. The Chinese traditional medicine system pharmacological database analysis platform (TCMSP) is the primary resource. The Traditional Chinese Medicine Integrated Database and Encyclopedia of Traditional Chinese Medicine database were used as secondary databases. The GeneCards database was used to search for reported tendinopathy-related genes by keywords. Functions of the targeted genes were analyzed using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes. Protein-protein interaction information was extracted from the STRING database. Docking study, MTT assay, quantitative real-time PCR, and migration assays were performed to obtain a better understanding of the herbs according to cell function to test the basic pharmacological action in vitro. A total of 104 disease nodes, 496 target gene nodes, 35 ingredient nodes, and one drug node were extracted. According to the TCMSP database, 6-hydroxykaempferol, which reportedly promotes the proliferation of microvascular endothelial cells, is a molecule found in SHT. We found that it promoted the proliferation and migration of tendon fibroblasts and elevated tendon repair-related gene expression. Purified 6-hydroxykaempferol promoted the proliferation and migration of tendon fibroblasts and increased their mRNA expression in tendon proliferation.

Clinical outcomes of anterior tibiofibular ligament's distal fascicle transfer versus ligament reconstruction with InternalBrace™ for chronic ankle instability patients.

PURPOSE: Treatment of chronic ankle instability (CAI) for ankle sprain patients remains a challenge. If initial treatments fail, surgical stabilization techniques including ligament reconstruction should be performed. Anterior tibiofibular ligament (ATiFL) distal fascicle transfer for CAI was recently introduced. The goal of the study is to assess the 1-year clinical effectiveness of ATiFL's distal fascicle transfer versus ligament reconstruction with InternalBrace™ (Fa. Arthrex, Naples). METHODS: Between October 2019 and February 2021, 25 patients (14 males and 11 females) scheduled for ligament reconstruction treatment of CAI were enrolled after propensity score matching. Twelve underwent ligament reconstruction with InternalBrace™ (InternalBrace™ group) and thirteen underwent ATiFL's distal fascicle transfer (ATiFL's distal fascicle transfer group). We recorded the American Orthopedic Foot & Ankle Society (AOFAS) score, Visual Analogue Scale (VAS), anterior drawer test grade, patient satisfaction and complications. All results of this study were retrospectively analyzed. RESULTS: Statistically significant (p = 0.0251, independent-samples t test) differences in the AOFAS can be found between the ATiFL's distal fascicle transfer group and the InternalBrace™ group. No substantial changes in the VAS (p = 0.1778, independent-samples t test), patient satisfaction (p = 0.1800, independent-samples t test) and anterior drawer test grade (p = 0.9600, independent-samples t test) were found between the two groups. There was one patient with superficial wound infection and one patient with sural nerve injury in the InternalBrace™ group and ATiFL's distal fascicle transfer group, respectively. CONCLUSION: This is the first study that assessed a cohort of CAI patients and suggests that the ATiFL's distal fascicle transfer operation has the potential to attain good-to-excellent clinical outcomes after 1-year recovery. The AOFAS scores were significantly higher for patients with ATiFL's distal fascicle transfer, indicating that this technique may be considered a viable option for both patients and their surgeon, while long-term outcomes should be investigated in the future.

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling.

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

Arthroscopic Hip Surgery versus Conservative Therapy on Femoroacetabular Impingement Syndrome: A Meta-Analysis of RCTs.

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

Comparing Surgical and Conservative Treatment on Achilles Tendon Rupture: A Comprehensive Meta-Analysis of RCTs.

Background: The Achilles tendon is the strongest tendon in human and is frequently injured, mainly in the young to middle age active population. Increasing incidence of Achilles tendon rupture (ATR) is still reported in several studies. Surgical repair and conservative treatment are two major management strategies widely adopted in ATR patients, but the consensus of the optimal treatment strategy is still debated. We aimed at thoroughly reviewing the ATR topic with additional assessments and performed a most comprehensive meta-analysis of randomized controlled trials (RCTs). Method: We comprehensively searched PubMed, Embase, Cochrane, and ClinicalTrial.gov and retrieved all RCTs comparing surgical and conservative treatment on ATR for further analysis. Two independent reviewers performed data extraction and random effect model was adopted when I 2 > 50%, with data presentation of risk ratio, risk difference, or mean difference and 95% confidence interval. Results: A total of 13 RCTs were included in this meta-analysis. A significant difference was observed in re-rupture, complication rate, adhesion to the underlying tendon, sural nerve injury, and superficial infection. A substantial reduction in re-rupture rate could be observed for surgical treatment while the complication rate was higher compared with conservative treatment. Conclusion: Surgical treatment revealed significance in reducing the re-rupture rate but was associated with a higher complication rate, while conservative treatment showed similar outcomes with a lower complication rate. Collectively, we recommend conservative treatment if patients' status and expectations are suitable, but surgeon and physician discretion is also crucial in decision making.

Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model.

OBJECTIVES: The objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)-induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model. METHODS: The rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A-treated 4-week group; the BTX-A-treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1ß level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro-computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}. RESULTS: BTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A-injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1ß level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume â€‹and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X-positive chondrocytes caused by muscle atrophy. CONCLUSIONS: Quadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.

Open versus arthroscopic ankle arthrodesis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is a growing health concern that affects approximately 27 million people in the USA and is associated with a $185 billion annual cost burden. Choosing between open surgery and arthroscopic arthrodesis for ankle arthritis is still controversial. This study compared arthroscopic arthrodesis and open surgery by performing a systematic review and meta-analysis. METHODS: For the systematic review, a literature search was conducted in 4 English databases (PubMed, Embase, Medline and the Cochrane Library) from inception to February 2020. Three prospective cohort studies and 7 retrospective cohort studies, enrolling a total of 507 patients with ankle arthritis, were included. RESULTS: For fusion rate, the pooled data showed a significantly higher rate of fusion during arthroscopic arthrodesis compared with open surgery (odds ratio 0.25, 95% CI 0.11 to 0.57, p = 0.0010). Regarding estimated blood loss, the pooled data showed significantly less blood loss during arthroscopic arthrodesis compared with open surgery (WMD 52.04, 95% CI 14.14 to 89.94, p = 0.007). For tourniquet time, the pooled data showed a shorter tourniquet time during arthroscopic arthrodesis compared with open surgery (WMD 22.68, 95% CI 1.92 to 43.43, p = 0.03). For length of hospital stay, the pooled data showed less hospitalisation time for patients undergoing arthroscopic arthrodesis compared with open surgery (WMD 1.62, 95% CI 0.97 to 2.26, p < 0.00001). The pooled data showed better recovery for the patients who underwent arthroscopic arthrodesis compared with open surgery at 1 year (WMD 14.73, 95% CI 6.66 to 22.80, p = 0.0003). CONCLUSION: In conclusion, arthroscopic arthrodesis was associated with a higher fusion rate, smaller estimated blood loss, shorter tourniquet time, and shorter length of hospitalisation than open surgery.

Ginsenoside Rb1/TGF-ß1 loaded biodegradable silk fibroin-gelatin porous scaffolds for inflammation inhibition and cartilage regeneration.

Creating a microenvironment with low inflammation and favorable for the chondrogenic differentiation of endogenous stem cells plays an essential role in cartilage repairing. In the present study, we design a novel ginsenoside Rb1/TGF-ß1 loaded silk fibroin-gelatin porous scaffold (GSTR) with the function of attenuating inflammation and promoting chondrogenesis. The scaffold has porous microstructure, proper mechanical strength, degradation rate and sustained release of Rb1 and TGF-ß1. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) seeded into GSTR scaffolds are homogeneously distributed and display a higher proliferation rate than non-loaded scaffolds (GS). GSTR scaffolds promote the chondrogenic differentiation of rBMSCs and suppress the expression of inflammation genes. Under the stimulation of IL-1ß, the inflammation level of the chondrocytes seeded in GSTR scaffolds is also significantly down-regulated. Moreover, GSTR scaffolds implanted into the osteochondral defects in rats effectively promote the regeneration of hyaline cartilage 12 weeks after surgery when compared with other groups. It is demonstrated that this scaffold loaded with Rb1 and TGF-ß1 can synergistically create a microenvironment favorable for cartilage regeneration by promoting the chondrogenesis and suppressing the inflammation levels in vivo. These results prove it has a great potential to develop this Rb1/TGF-ß1 releasing scaffold into a novel and promising therapeutic for cartilage repair.

Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1ß. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1ß. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.

Sustained Release SDF-1α/TGF-ß1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair.

Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1α (SDF-1α)/transforming growth factor-ß1 (TGF-ß1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1α and TGF-ß1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1α and TGF-ß1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-ß1-loaded scaffolds (GSTS or GST: loading TGF-ß1 only) and the conditioned medium from SDF-1α-loaded scaffolds (GSTS or GSS: loading SDF-1α only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1α and TGF-ß1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1α and TGF-ß1 releasing GSTS have promising therapeutic potential in cartilage repair.

Long form collapsin response mediator protein-1 promotes the migration and invasion of osteosarcoma cells.

It has been reported that long form collapsin response mediator protein-1 (LCRMP-1) promotes the metastasis of non-small cell lung cancer. Osteosarcoma (OS) is a human cancer with a high potential for metastasis. The present study aimed to investigate the role of LCRMP-1 in OS metastasis. The expression of LCRMP-1 in OS specimens and cell lines was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Furthermore, the migration and invasion of OS cells with LCRMP-1-knockdown was investigated to examine the role of LCRMP-1 in OS metastasis. In addition, the expression of N-cadherin and matrix metalloproteinases (MMPs), which are involved in cell migration, was evaluated using RT-qPCR. Increased expression of LCRMP-1 was observed in the OS tissues and cell lines, accompanied by the enhanced migration and invasion of the OS cells. LCRMP-1-knockdown resulted in a significant decrease in the expression of N-cadherin and MMPs, as well as inhibition of the migration and invasion of the OS cells. Overexpression of LCRMP-1 promoted OS metastasis. Therefore, LCRMP-1 may be a promising target for the effective treatment of OS.

[A comparative study between humeral head prosthesis replacement and internal fixation for treatment of comminuted proximal humeral fractures].

OBJECTIVE: To compare the clinical efficacies of humeral head prosthesis and internal fixation in the treatment of comminuted proximal humeral fractures. METHODS: The clinical data were analyzed for the patients with comminuted proximal humeral fractures undergoing surgeries for humeral head replacement or open reduction plus internal fixation in our hospital between January 2002 and January 2009. Constant scores were used to determine the excellent clinical outcome rates in the two groups, and the operating time, blood loss and postoperative motor scores of the shoulder were compared. RESULTS: Forty patients in the humeral head replacement group were evaluated. According to the Constant scores, excellent outcomes were achieved in 16 patients, good outcomes in 18 patients, moderate in 3 patients, and poor in 3 patients, with an excellent outcome rate of 85%. In the 40 cases receiving open reduction plus internal fixation, excellent outcomes were achieved in 11 cases, good in 13 cases, moderate in 8 cases, and poor in 8 cases, with an excellent clinical outcome rate of 60%. Compared with open reduction plus internal fixation, humeral head replacement was associated with shortened operating time, reduced blood loss and better motor function recovery of the shoulder. CONCLUSIONS: Replacement of humeral head prosthesis produces better clinical outcomes than open reduction and internal fixation in patients with comminuted proximal humeral fractures, and can promote the short-term functional recovery of the shoulder with minimal surgical complications.