Effects of vegetation degradation on soil microbial communities and ecosystem multifunctionality in a karst region, southwest China.

Vegetation degradation caused by intense human disturbances poses a significant challenge to the preservation and improvement of ecosystem functions and services in the karst region of southwest China. Soil microorganisms are major regulators of ecosystem multifunctionality (EMF). Currently, there is a dearth of knowledge regarding the effects of vegetation degradation on soil microbial communities and their corresponding multiple ecosystem functions in karst regions. In this study, we selected the vegetation degradation sequences of second natural forest (NF), agroforestry (AS) and cropland (CL) to investigate the diversity of bacterial, fungal and protistan communities, and their hierarchical co-occurrence network, and EMF to explore the relationships between them. Compared to the NF, the carbon cycling index, nitrogen cycling index, soil water regulation power, and the EMF were significantly decreased by 8.2%-50.6%, 48.7%-86.8%, 19.8%-24.5%, and 31.4%-69.5% in the AS and CL, respectively. The development of EMF can be explained by the fungal, protistan and microbial hierarchical ß-diversity, as well as the complexity (e.g. degree) of microbial hierarchical interactions during the process of vegetation degradation. Notably, correlations between the abundances of sensitive amplicon sequence variants (sASVs) for different karst vegetation types and EMF varied in distinct network modules, being positive in module 1 and negative in module 2. Moreover, the relative abundance of keystone taxa in fungal and protistan communities provided greater contributions to EMF than the bacterial communities. Additionally, random forest modeling showed that carbon and nitrogen sources, and soil water content, and trace elements (e.g. exchangeable magnesium, iron, manganese, and zinc) were identified as key driving factors of the EMF. Collectively, our findings demonstrate that vegetation degradation obviously alters soil microbial diversities and hierarchical interactions, emphasizing their key role in maintaining ecosystem functions and health in karst regions.

Efficacy of rotator cuff suture and arthroscopic 360° capsular release in patients with rotator cuff tear with limited shoulder movement.

BACKGROUND: To determine the clinical efficacy of rotator cuff suture and arthroscopic 360° capsular release in patients with rotator cuff tendinopathy to improve the Constant-Murley and Visual Analogue Scale (VAS) scores, and shoulder flexion. METHODS: Fifty-one patients with full-thickness rotator cuff tears and limited shoulder movement who were admitted to our hospital from October 2017 to October 2020 were selected; all patients were treated with arthroscopic rotator cuff suture and 360° capsular release. The Constant-Murley score, VAS score, and shoulder flexion angle were used to evaluate shoulder joint function before and during follow-up. Rotator cuff healing was assessed by MRI with the Sugaya classification. RESULTS: After treatment, the Constant-Murley score (58.98 ± 9.84) was significantly improved compared with pre-treatment (29.33 ± 9.71), the VAS score (1.23 ± 0.87) was significantly lower than pre-treatment (7.54 ± 1.22), and the shoulder flexion angle (142.67 ± 8.59°) was significantly improved compared with pre-treatment (51.50 ± 2.10°); the difference was statistically significant (P < 0.05). CONCLUSIONS: Arthroscopic rotator cuff suture and simultaneous 360° capsular release have a significant effect on the treatment of rotator cuff tear with limited shoulder movement.

Multifunctional injectable hydrogel for effective promotion of cartilage regeneration and protection against osteoarthritis: combined chondroinductive, antioxidative and anti-inflammatory strategy.

The regeneration of the articular cartilage defects is characterized by the improvement in the quality of the repaired tissue and the reduction in the potential development of perifocal osteoarthritis (OA). Usually, the injection of dexamethasone (Dex) in the OA joints slows down the progression of inflammation and relieves pain. However, the anti-inflammatory Dex injected in the joint cavity is rapidly cleared, leading to a poor therapeutic effect. Multifunctional hydrogels with simultaneous chondrogenic differentiation, antioxidative, and anti-inflammatory capacities may represent a promising solution. Therefore, in this work, a novel injectable hydrogel based on double cross-linking of Schiff base bonds and coordination of catechol-Fe was developed. The obtained hydrogel (Gel-DA/DOHA/DMON@Dex@Fe) possessed molding performance in situ, excellent mechanical strength, controllable biodegradability, the on-demand release of the drug, and biocompatibility. The hydrogel system stimulated the HIF-1α signaling pathway and suppressed inflammation thanks to the introduction of DMON@Fe, consequently facilitating chondrogenic differentiation. The synergistic anti-inflammatory effect together with the induction of chondrogenesis by Dex-loaded Gel-DA/DOHA/DMON@Fe hydrogel allowed the promotion of cartilage repair, as demonstrated by in vivo experiments. Hence, the proposed multifunctional scaffold provides a promising advancement in articular cartilage tissue engineering and may have great prospects in the prevention of OA.

The effect of post-operative limb positioning on blood loss and early outcomes after primary total knee arthroplasty: a randomized controlled trial.

INTRODUCTION: The purpose of this study was to investigate the benefits of three different post-operative limb positions in primary total knee arthroplasty (TKA). METHODS: The trial was a single-surgeon, randomized, controlled trial, and 135 patients following primary TKA were randomized into three groups: group A (45 patients who were treated with the hip fixed at 50° and knee flexed at 90° for 6 hours post-operatively), group B (45 patients who were treated with the hip elevated at 30° and knee flexed at 45° for 6 hours  post-operatively), and group C (45 patients in whom the affected knee was fully extended after surgery). Tranexamic acid was used in all patients. RESULTS: The total blood loss and hidden blood loss in group A (921 ± 209 mL, 597 ± 213 mL) were significantly less than in groups B (1125 ± 222 mL, 784 ± 229 mL) and C (1326 ± 291 mL, 915 ± 301 mL) and less in group B compared with group C. The drain volume in groups A (158 ± 35 mL) and B (174 ± 45 mL) was significantly lower than in group C (249 ± 31 mL). The maximum haemoglobin drop in group A (3.1 ± 0.5 g/dL) was statistically significantly less than in groups B (3.6 ± 0.7 g/dL) and C (4.3 ± 0.4 g/dL). The range of motion (ROM) in groups A (102 ± 3°, 105 ± 2°) and B (100 ± 3°, 104 ± 2°) was significantly better than in group C (98 ± 3°, 102 ± 2°) at the time of discharge and one  month after surgery; it was also significantly less for group A (104.9 ± 2.1%, 108.0 ± 2.4%) compared with groups B (106.7 ± 3.1%, 108.3 ± 2.7%) and C (108.4 ± 3.2%, 110.6 ± 3.0%) with post-operative knee swelling. No differences in transfusion requirements and complications were observed among the three groups. CONCLUSIONS: The affected knee flexion position was superior to the use of a fully extended position for blood management, but it only contributed to better early functional recovery up to three  months post-operatively in TKA. In addition, by fixing the affected knee at a high flexion position of 90°, patients could achieve less blood loss, lower knee swelling, and better early results for ROM and patient satisfaction than the other two groups.

Effect of knee flexion position and combined application of tranexamic acid on blood loss following primary total knee arthroplasty: a prospective randomized controlled trial.

PURPOSE: The aim of this study was to demonstrate the association between tranexamic acid (TXA)-combined application and knee flexion in the first 24 hour post-operatively that could reduce total blood loss and transfusion need in patients undergoing total knee arthroplasty (TKA), without sacrificing safety. METHODS: Ninety TKA patients were divided into three groups randomly: the flexion group: the knee was in 90° flexion position for the first 12 hour post-surgery and kept at 60°for the next 12 hour, combined with 1 g TXA topical and 1 g TXA intravenous application. The extension group: the knee was in fully extension position post-operatively, combined with topical and intravenous TXA application. The controlled group: the knee was in fully extension position post-operatively combined with single intravenous TXA application. The primary outcomes included blood loss variables and transfusion values. The secondary outcomes included post-operative hospital stay, knee flexion degree, complication rate, and hospital charge. RESULTS: The total blood loss and transfusion needs in the flexion group were significantly reduced in comparison with that in the extension group and controlled group. The post-operative knee flexion motion was significant higher in the flexion group than the other two groups. There was no difference among the three groups with regard to the rates of complications. CONCLUSIONS: Keeping the knee in flexion position combined with topical and intravenous TXA application in patients undergoing primary unilateral TKA significantly reduced post-operative bleeding and the transfusion rate compared with what was found after treatment with extension knee position or single intravenous TXA application. LEVEL OF EVIDENCE: Therapeutic Level I.

WITHDRAWN: The Congruence and Joint Space Width of the Lateral Compartment Can Be Restored After Medial Unicompartmental Knee Arthroplasty.

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Patients achieved greater range of movement when using high-flexion implants.

PURPOSE: NexGen Legacy Posterior Stabilized high-flexion prostheses (LPS-Flex) have been popularized as an alternative to NexGen standard prostheses (LPS) in total knee arthroplasty (TKA). Advocates of this new generation prosthesis suggest improved postoperative knee flexion. The purpose of this study was to summarize the best evidence for comparing the range of motion (ROM) and functional outcomes of LPS-Flex prostheses and LPS in TKA. METHODS: Electronic databases were systematically searched to identify relevant randomized controlled trials (RCTs). The last date for our research was July 2014. Our search strategy was followed the requirements of the Cochrane Library Handbook. The methodological quality was assessed, and the data were extracted independently by two authors. RESULTS: Nine studies that included 978 knees met our inclusion criteria for review. The results showed that there was larger postoperative ROM (1.62, 95% CI 0.52-2.72) in the LPS-Flex group than in the LPS group. There was not a statistically significant difference in the clinical functional scores and complications between the LPS-Flex group and the LPS group in TKA. The pooled mean differences were as follows: total KSS, -0.64 (95% CI -1.41 to 0.13); functional KSS, -0.53 (95% CI -1.51 to 0.45); HSS, 0.23 (95% CI -0.87 to 1.33); complications, 0.49 (95% CI 0.20-1.24); and radiolucent lines, 1.56 (95% CI 0.68-3.55). CONCLUSIONS: The preliminary results indicate that the NexGen LPS-Flex prosthesis provides an alternative to the NexGen LPS prosthesis, with greater range of motion and without severe complications or radiographic outcomes. The clinical advantages were not shown in the KSS or the HSS. Thus, the selection of a high-flexion prosthesis should depend on the characteristics of the patient, particularly high motivation and poor preoperative ROM. The potential benefits in the medium- and long-term outcomes require confirmation by larger, multicenter and well-conducted RCTs. LEVEL OF EVIDENCE: Therapeutic study, Level I.

A meta-analysis of minimally invasive and conventional medial parapatella approaches for primary total knee arthroplasty.

PURPOSE: Minimally invasive surgical (MIS) approaches for total knee arthroplasty (TKA) have become increasingly popular for doctors and patients. They have argued that it decreases post-operative pain, accelerates functional recovery and increases patient satisfaction due to less injury. However, critics are concerned about TKA's possible effects on component position and with complications, considering the procedure's limited exposure. The purpose of this study was to summarise the best evidence in comparing the clinical and radiological outcomes between MIS and a conventional approach in TKA. METHODS: Electronic databases were systematically searched to identify relevant randomised controlled trials (RCTs). Our search strategy followed the requirements of the Cochrane Library Handbook. Methodological quality was assessed, and data were extracted independently by two authors. RESULTS: Thirty studies, including 2,536 TKAs, were reviewed: 1,259 minimally invasive and 1,277 conventional exposure TKAs. The results showed that while the MIS group had longer operation times and tourniquet times, it had superior outcomes in KSS (objective and total), range of motion, flexion range of motion, flexion 90° day, straight leg-raising day, total blood loss and decrease in haemoglobin. However, wound-healing problems occurred more frequently in the MIS group. There were no statistically significant differences in other clinical or radiological outcomes between the MIS and conventional groups in TKA. CONCLUSION: The preliminary results indicate that the MIS approach provides an alternative to the conventional approach, with earlier rehabilitation but no malpositioning or severe complications. Wound-healing problems can be treated easily and effectively, and the risk also decreases as surgeons become more experienced, and more user-friendly instruments are invented. Potential benefits in medium- and long-term outcomes require larger, multicentre and well-conducted RCTs to confirm. LEVEL OF EVIDENCE: Therapeutic study, Level II.

Do patients really gain outcome benefits when using the high-flex knee prostheses in total knee arthroplasty? A meta-analysis of randomized controlled trials.

The purpose of this study was to undertake a meta-analysis to evaluate whether patients really gain outcome benefits when using the high-flex (HF) prostheses in total knee arthroplasty (TKA) compared with standard (STD) implants. Only randomized controlled trials were included in this meta-analysis. After searching PubMed, Embase, Wed of Science and Cochrane Library, 1042 papers were identified and 18 trials were finally eligible for meta-analysis including 2069 knees (1906 patients). We found no statistically significant difference between the two designs in terms of ROM, knee scores (KSS, HSS, WOMAC, and SF-36), patients' satisfaction and complications. Hence there is currently no evidence to confirm that the use of high-flex prostheses in short-term is superior to the standard prostheses after total knee arthroplasty.

Over-the-Top Double-Bundle Revision Anterior Cruciate Ligament Reconstruction Technique With Hybrid Hamstring Tendon Autograft-Allograft and Associated Lateral Extra-articular Tenodesis.

Revision anterior cruciate ligament (ACL) presents many technical challenges that are not commonly seen in primary ACL reconstruction. The purpose of this article is to describe an alternative technique consisting of over-the-top double-bundle ACL revision combined with lateral extra-articular tenodesis using hybrid hamstring tendon autograft-allograft. This technique provides a valid treatment option in ACL revision surgery.

Arthroscopic fixation techniques for tibial eminence fractures in pediatric patients: a review.

The introduction of new internal fixation devices and arthroscopic techniques has led to significant changes in the surgical treatment of tibial eminence fractures (TEFs) in children. In recent years, arthroscopic surgery has arisen as the gold standard for the treatment of TEFs. This popularity of arthroscopic techniques has reduced surgical complications and improved patient prognosis. In this paper, we investigate the current situation of the use of arthroscopic fixation techniques for pediatric TEFs. We searched the PubMed database using the terms "arthroscopic treatment and tibial eminence," "arthroscopic treatment and tibial spine," "tibial eminence avulsion", "tibial spine fracture", with no limit on the year of publication. From these articles, we reviewed the use of various arthroscopic TEFs fixation techniques reported in the current literature. Overall, we found that the choice of fixation method seems to have no effect on clinical outcomes or imaging results. However, if an easy, strong fixation that is less prone to epiphyseal damage is desired, as a junior practitioner, the anchor technique should be mastered first, whereas for senior practitioners, a variety of fixation techniques for TEFs should be mastered, including anchors, sutures, and screws, so that personalized fixation can be achieved with the least amount of trauma, operative time, and complications. Higher quality studies are needed in the future to provide Useful evidence to determine the optimal fixation technique in terms of clinical outcomes, function, and complications.

RETRACTED: Chen et al. Clinical Effect of Arthroscopic Resection of Extra-Articular Knee Osteochondroma. J. Clin. Med. 2023, 12, 52.

Following publication, the authors of "Clinical Effect of Arthroscopic Resection of Extra-Articular Knee Osteochondroma" by Chen et al. [...].

[Effectiveness of arthroscopic distal clavicle resection for symptomatic acromioclavicular joint arthritis].

Objective: To investigate the effectiveness of arthroscopic distal clavicle resection for the symptomatic acromioclavicular joint arthritis. Methods: The clinical data of 14 patients with symptomatic acromioclavicular joint arthritis treated by arthroscopic indirect distal clavicle resection between January 2020 and March 2021 were retrospectively analyzed. There were 5 males and 9 females with an average age of 46.3 years (range, 18-57 years). The 4 cases of left shoulder and 10 cases of right shoulder were accompanied with acromial impingement, without the history of shoulder trauma. The average disease duration was 20.4 months (range, 9-48 months), and the average visual analogue scale (VAS) score was 7.6 (range, 5-9) preoperatively. The results were evaluated using the University of California Los Angeles (UCLA) shoulder rating score before and after operation, further, the patient satisfaction rate was also calculated. Results: All 14 patients were followed up 5-18 months, with an average of 13 months. There was no postoperative pain of acromioclavicular joint in 12 patients; 1 case had occasional mild pain, which could be controlled by painkillers. Moreover, there was only 1 acromioclavicular joint subluxation due to early fitness training at 2 weeks postoperatively, and the symptoms gradually relieved after 1 month of conservative treatments. The UCLA score was 22.1±6.2 preoperatively, which improved to 30.2±3.4 at last follow-up, showing significant difference ( t=5.359, P<0.001). The patient satisfaction rate was 92.9%, with 12 excellent cases, 1 good case, and 1 fair case. Conclusion: Arthroscopic distal clavicle resection for symptomatic acromioclavicular arthritis is a safe, reliable, and repeatable procedure.

Clinical Effect of Arthroscopic Resection of Extra-Articular Knee Osteochondroma.

Objective: The aim of this study was to investigate clinical outcomes of arthroscopic resection of extraarticular knee osteochondroma. Methods: A retrospective analysis was performed in 74 patients with extra-articular knee osteochondroma treated by arthroscopic resection between August 2011 and August 2021, including 43 males and 31 females. Overall, 26 Distal femur cases and 48 proximal tibia cases were involved, with an average age of 31.7 ± 11.3 (11−57) years. Preoperative routine knee X-ray, CT, and MRI were performed before the operation. The Lysholm knee score, International Knee Documentation Committee (IKDC) score, Tegner knee motor function score, and visual analogue scale (VAS) were used to evaluate symptoms and functions before surgery and 3, 6, 12, and ≥24 months after surgery. Results: The average course of disease was (7.9 ± 3.7) months (range, 3−14 months) in 74 patients. The average follow-up was (22.6 ± 6.4) months (range, 10−37 months). There were no cases of vascular or nerve injury or wound infection. Compared with the preoperative function, the average scores of VAS, Lysholm, IKDC, and Tegner joint motor function decreased or increased significantly compared with the last follow-up (3.6 ± 1.1 vs. 0.1 ± 0.02, 44.5 ± 2.3 vs. 91.3 ± 4.9, 53.7 ± 2.6 vs. 94.2 ± 5.1, 4.6 ± 1.2 vs. 9.4 ± 1.4, p < 0.001). There was no recurrence or metastasis during the follow up. Conclusions: With the advantages of less trauma, high precision, less pain, and rapid recovery, arthroscopic resection of extra-articular knee osteochondroma can significantly improve the function of knee. It can be gradually extended to the treatment of other benign bone tumors.

Deep Learning-Based Magnetic Resonance Imaging Image Features for Diagnosis of Anterior Cruciate Ligament Injury.

To study and explore the adoption value of magnetic resonance imaging (MRI) in the diagnosis of anterior cruciate ligament (ACL) injuries, a multimodal feature fusion model based on deep learning was proposed for MRI diagnosis. After the related performance of the proposed algorithm was evaluated, it was utilized in the diagnosis of knee joint injuries. Thirty patients with knee joint injuries who came to our hospital for treatment were selected, and all patients were diagnosed with MRI based on deep learning multimodal feature fusion model (MRI group) and arthroscopy (arthroscopy group). The results showed that deep learning-based MRI sagittal plane detection had a great advantage and a high accuracy of 96.28% in the prediction task of ACL tearing. The sensitivity, specificity, and accuracy of MRI in the diagnosis of ACL injury was 96.78%, 90.62%, and 92.17%, respectively, and there was no considerable difference in contrast to the results obtained through arthroscopy (P > 0.05). The positive rate of acute ACL patients with bone contusion and medial collateral ligament injury was substantially superior to that of chronic injury. Moreover, the incidence of chronic injury ACL injury with meniscus tear and cartilage injury was notably higher than that of acute injury, with remarkable differences (P < 0.05). In summary, MRI images based on deep learning improved the sensitivity, specificity, and accuracy of ACL injury diagnosis and can accurately determined the type of ACL injury. In addition, it can provide reference information for clinical treatment plan selection and surgery and can be applied and promoted in clinical diagnosis.

Circ_HECW2 regulates LPS-induced apoptosis of chondrocytes via miR-93 methylation.

INTRODUCTION: Circ_HECW2 plays a key role in lipopolysaccharide (LPS)-induced signal transduction, which is critical in osteoarthritis (OA). Thus, we analyzed the role of Circ_HECW2 in osteoarthritis. METHODS: The expression of Circ_HECW2 and miR-93 was examined using reverse-transcription polymerase chain reaction. Cell apoptosis was evaluated using Annexin V-FITC Apoptosis Detection Kit. RESULTS: Circ_HECW2 and miR-93 were inversely correlated, with Circ_HECW2 upregulated and miR-93 downregulated in OA and LPS-induced chondrocytes. Circ_HECW2 overexpression inhibited miR-93 expression and increased methylation of miR-93 coding gene. Cell apoptosis analysis showed that Circ_HECW2 overexpression increased LPS-induced chondrocyte apoptosis, while MiR-93 overexpression reversed the effects of Circ_HECW2 on chondrocyte apoptosis. CONCLUSION: In summary, our data revealed that the Circ_HECW2 is highly expressed in OA and might inhibit miR-93 expression through methylation to affect LPS-induced chondrocyte apoptosis.

A Bone-Hamstring Autograft for Arthroscopic Anterior Cruciate Ligament Reconstruction.

We describe a bone-hamstring autograft for anterior cruciate ligament reconstruction (ACLR). The semitendinosus and gracilis tendons are harvested using an open tendon stripper, keeping these distal tibial insertions intact. The bone-hamstring autograft is harvested using an oscillating saw. This modified autograft has the following advantages: (1) It possesses the potential for healing with the femur owing to its bone plug; (2) it is perfectly suited for various single-bundle reconstruction methods including oval-tunnel and rectangular-tunnel ACLR, as well as other flat ACLR methods; and (3) it is an attractive option for both primary ACLR and revision ACLR owing to its unique characteristics.

The effect of running on knee joint cartilage: A systematic review and meta-analysis.

OBJECTIVE: Although running causes inevitable stress to the joints, data regarding its effect on the cartilage of the knee are conflicting. This systematic review and meta-analysis aimed to evaluate the effect of running on knee joint cartilage. METHODS: PubMed, EMBASE, SportDiscus, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) and cohort studies. The outcome indicators were cartilage oligomeric matrix protein (COMP), cartilage volume and thickness, and T2. RESULTS: A total of two RCTs and 13 cohort studies were included. There was no significant difference in cartilage volume between the running and control groups (MD, -115.88 U/I; 95% CI, -320.03 to 88.27; p = 0.27). However, running would decrease cartilage thickness (MD, -0.09 mm; 95%CI, -0.18 to -0.01; p = 0.03) and T2 (MD, -2.78 ms; 95% CI, -4.12 to -1.45; p < 0.001). Subgroup analysis demonstrated that COMP immediately or at 0.5 h after running was significantly increased, but there were no significant changes at 1 h or 2 h. CONCLUSIONS: Running has advantages in promoting nutrition penetrating into the cartilage as well as squeezing out the metabolic substance, such as water. Our study found that running had a short-term adverse effect on COMP and did not affect cartilage volume or thickness.

Gene Therapy with Tetracycline-Regulated Human Recombinant COLIA1 cDNA Direct Adenoviral Delivery Enhances Fracture Healing in Osteoporotic Rats.

A number of previous studies have indicated that the genetic variation at the collage type I alpha 1 (COLIA1) gene locus influences susceptibility to osteoporosis. However, seldom have studies reported the effect of gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA on stimulating osteogenic activity of osteoblasts and enhancing fracture healing of ovariectomized rats. The current study was performed to demonstrate whether direct gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA could stimulate osteogenic activity of osteoblast in vitro and enhance fracture healing of ovariectomized rats in vivo. In vitro, the tet-on system regulated COLIA1 gene adenovirus was constructed and transfected to osteoblasts. COLIA1 mRNA and collagen type I levels were assessed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay to determine whether adenovirus transfected successfully. Osteogenic activity of the osteoblasts was assessed by alkaline phosphatase activity, immunohistochemical staining, immunofluorescent staining, mineralized matrix formation, and extracellular calcium levels. In vivo, adenovirus-delivered COLIA1 gene was injected into the fracture site of the tibia in an ovariectomized rat model of osteoporosis, and bone callus condition was assessed to determine whether the COLIA1 gene could accelerate osteoporotic fracture healing. In vitro, the results showed that COLIA1 gene adenovirus transfection could increase osteoblast COLIA1 gene expression and collagen type I protein synthesis, increase alkaline phosphatase activity, and stimulate calcium nodules formation, which exhibited a direct osteogenic effect on the osteoblasts. In vivo, local injection of COLIA1 gene adenovirus increased collagen type I expression, restored bone mineral density, and accelerated fracture healing in ovariectomized rats, without increasing serum collagen type I and liver COLIA1 mRNA levels. This study suggests direct gene delivery using an adenovirus carrying human COLIA1 cDNA can stimulate the osteogenic activity of osteoblasts in vitro and enhance bone fracture healing in vivo. The tet-on system is an ideal gene regulatory system for effective and safe regulation of the therapeutic gene.

MicroRNA-140 Suppresses Human Chondrocytes Hypertrophy by Targeting SMAD1 and Controlling the Bone Morphogenetic Protein Pathway in Osteoarthritis.

BACKGROUND: This study aimed to investigate the expression levels and relationship of bone morphogenetic proteins (BMPs) signaling molecules and microRNA-140 (miR-140) in human osteoarthritis (OA) chondrocytes. MATERIALS AND METHODS: Different stage chondrocytes (normal cartilage, mid-stage OA and advanced-stage OA) were isolated from cartilage samples according to Kellgren and Lawrence criteria. The effect of miR-140 on BMPs signaling was evaluated by transfecting miR-140 mimic or inhibitor into chondrocytes. The expression of responsive genes was measured using real-time polymerase chain reaction and Western blotting analysis. RESULTS: There was a significant reduction in miR-140 and SOX9 expression in OA groups compared to the normal group, and there was a further reduction in the severe OA group compared to the moderate OA group. Compared with the normal group, the expression of ALK1, SMAD1, COL10A1 and MMP3 was higher in the OA groups, whereas the expression of COL2A1 was lower in the OA groups. In the moderate OA group, transfection with miR-140 mimic increased SMAD1, SOX9 and COL2A1 expression, but decreased COL10A1 expression. However, there was an opposite effect after transfecting miR-140 inhibitor with decreased SMAD1, SOX9 and COL2A1 expression, and increased COL10A1 expression. Interestingly, the biological effect of transfecting miR-140 mimic or inhibitor was similar in the severe OA group. SMAD1 and COL2A1 protein production followed the same pattern as their expression profile. CONCLUSIONS: miR-140 suppresses chondrocytes hypertrophy by controlling the BMPs signaling pathway, which highlights the importance of miR-140 in the maintenance of chondrocyte homeostasis and opens up novel avenues in OA therapeutic strategies.