Negative effects of high mechanical tensile strain stimulation on chondrocyte injury in vitro.

The mechanism underlying the development of osteoarthritis induced by high tensile strain is unclear. In this study, the effects of different degrees of mechanical tensile strain stimulation on Sprague-Dawley rat chondrocytes were explored. Rat chondrocytes were subjected to mechanical tensile strain at different intensities and frequencies (control group, low tensile strain group, intermediate tensile strain group, and high tensile strain group) using a self-made in vitro tensile strain device. After applying mechanical tensile strain, chondrocytes were collected to detect the expression of collagen II, Aggrecan, matrix metalloproteinase 13 (MMP13), ADAMTS5, and uncoupling protein 2 (UCP2) by real-time quantitative PCR and western blotting as well as reactive oxygen species (ROS) by fluorescence probes. Mechanical tensile strain at different frequencies and intensities had different effects on the biological functions of chondrocytes. Compared with the control group, the expression levels of Col II and Aggrecan in the low and intermediate tensile strain groups increased significantly, while the expression of MMP13 and ADAMTS5 decreased. There were no significant differences between the low and intermediate tensile strain groups. Col II and Aggrecan levels were significantly lower in the high tensile strain group than in the control group, while MMP13 and ADAMTS5 levels were higher. There were no significant differences in ROS production between the low and intermediate tensile strain groups and the control group, but the high tensile strain group exhibited significantly increased ROS production. The expression of UCP2 was significantly lower in the high tensile strain group than in all other groups. These results showed that stimulation with different levels of mechanical tensile strain has different effects on chondrocytes. Repeated high tensile strain promoted the anabolic function of chondrocytes, increased ROS production, and decreased UCP2. These results provide a potential mechanism by which osteoarthritis is induced by high mechanical tensile strain.

A Probability Fusion Approach for Foot Placement Prediction in Complex Terrains.

Prediction of foot placement presents great potential in better assisting the walking of people with lower-limb disability in daily terrains. Previous researches mainly focus on foot placement prediction in level ground walking, however these methods cannot be applied to daily complex terrains including ramps, stairs, and level ground with obstacles. To predict foot placement in complex terrains, this paper presents a probability fusion approach for foot placement prediction in complex terrains which consists of two parts: model training and foot placement prediction. In the first part, a deep learning model is trained on augmented data to predict the probability distribution of preliminary foot placement. In the second part, environmental information and human walking constraints are used to calculate the feasible area, and finally the feasible area is fused with the probability distribution of preliminary foot placement to predict the foot placement in complex terrains. The proposed method can predict the foot placement of next step in complex terrains when heel-off is detected. Experiments (including structured terrains experiments and complex terrains experiments) show that the root mean square error (RMSE) of prediction is 8.19 ± 1.20 cm, which is less than 8% of the average stride length, and the landing feasible area accuracy (LFAA) of prediction is 95.11 ± 3.09%. Comparing with existing foot placement prediction studies, the method proposed in this paper achieves faster and more accurate prediction in complex terrains.

Adaptive Oscillator-Based Assistive Torque Control for Gait Asymmetry Correction With a nSEA-Driven Hip Exoskeleton.

Gait asymmetry is an important clinical characteristic of the hemiplegic gait most stroke survivors suffered, leading to restricted functional mobility and long-term negative impact on their quality of life. In recent years, robot assistance has been proven able to improve stroke patients' functional walking, but few studies have been conducted to specifically correct gait asymmetry of stroke patients during the whole gait cycle. In this work, an adaptive oscillator-based assistive torque control was developed and implemented on a unilateral hip exoskeleton driven by a novel nonlinear series elastic actuator (nSEA), aiming at correcting gait asymmetry at hip joints during the whole gait cycle. The adaptive oscillator-based gait asymmetry detection method extracted continuous gait phase and gait asymmetry seamlessly, and then the proposed assistive control attempted to correct gait asymmetry by delivering precise assistive torques synchronized with the continuous gait phase of the patients' gait. An initial experimental study was conducted to evaluate the proposed assistive control on seven healthy subjects with artificial impairment. The participants walked on a treadmill with assistance from the hip exoskeleton, while artificial impairment was added to mimic the hemiplegic gait with both spacial and temporal asymmetry (such as reduced hip flexion in the impaired side and reduced hip extension in the healthy side). Experimental results suggested the effectiveness of the proposed assistive control in restoring gait symmetry to levels comparable to a normal gait of the participants ( ).

Mutational Screening of Skeletal Genes in 14 Chinese Children with Osteogenesis Imperfecta Using Targeted Sequencing.

Background: As a heterogeneous hereditary connective tissue disorder, osteogenesis imperfecta (OI) is clinically characterized by increased fracture susceptibility. Analysis of genetic pathogenic variants in patients with OI provides a basis for genetic counseling and prenatal diagnosis. Methods: In this study, 14 diagnosed OI patients from sporadic Chinese families were enrolled to be screened for potential mutations from these patients by next-generation sequencing technology. Results: 34 different variants were identified. 18 variants were from 4 OI-related genes including COL1A1, COL1A2, P3H1, and WNT1, and 10 variants are novel. Most OI patients (11 out of 14, 78%) harbor variants in type I collagen genes. Conclusions: Our results support previously established estimates of the distribution and prevalence of OI mutations and highlight both phenotype and genetic heterogeneity among and within families. We report several novel variants of OI, which expands the clinical spectrum of OI. In summary, our data provides disease-causing genes information for genetic counseling towards OI patients and families and also provides a reference for clinicians in the diagnosis of OI, also in prenatal diagnosis of this disease.

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3.

BACKGROUND: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. METHODS: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. RESULTS: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. CONCLUSION: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.

Next­generation sequencing of miRNAs and lncRNAs from rat femur and tibia under mechanical stress.

Exercise intervention has become one of the most effective methods to prevent and treat osteoporosis, which is a common age­related disease and seriously affects the health and quality of life of the elderly. However, the molecular mechanism remains to be elucidated. The present study demonstrated the exercise­induced promotion of osteogenic differentiation and inhibition of adipogenic differentiation in femur and tibia by establishing an animal exercise model using a treadmill exercise system. MicroRNA (miRNA/miR) and long non­coding (lnc)RNA sequencing analyses identified 16 upregulated and two downregulated miRNAs in the exercise group, as well as 44 upregulated lncRNAs and 39 downregulated lncRNAs in the exercise group. There was increased expression of miR­9942 and miR­7704 in both the femur and tibia and an upregulation of miR­30d, miR­5100 and miR­1260 in the femur of animals from the exercise group. In addition, four of the five most downregulated lncRNAs, including lncRNA MSTRG.2625, lncRNA MSTRG.1557, lncRNA MSTRG.691 and lncRNA MSTRG.7497, were demonstrated to be suppressed in both the femur and tibia after treadmill exercise. The results of the present study provided a valuable resource for further exploring the molecular mechanisms underlying the regulation of osteoporosis by exercise.

Percutaneous fixation of neonatal humeral physeal fracture: A case report and review of the literature.

BACKGROUND: Neonatal distal humeral physeal fractures are rare and difficult to diagnose. Thus, missed diagnoses and delayed healing are possible. Few studies have reported surgical treatment, because a callus may develop at the fracture site 5 d after the fracture, resulting in difficult reduction, and reduction of the limb may cause further physeal injury. Other surgical challenges include the provision of adequate anesthesia and complexity of the operation. However, without appropriate reduction and fixation, a varus elbow deformity may develop. Manual reduction and percutaneous pin fixation are ideal treatment options. CASE SUMMARY: A 4-day-old neonate with left elbow pain accompanied by limited movement for 4 d was admitted, and diagnosed with delayed physeal fracture of the distal humerus based on physical examination, ultrasonography, and magnetic resonance imaging. The patient was treated by manual reduction combined with percutaneous pin fixation under arthrography. Postoperatively, the reduction was successful. The upper limbs could have been lifted and the fingers could have been moved freely on the second day after the operation. CONCLUSION: The techniques of manual reduction and percutaneous pin fixation, to treat neonatal distal humeral physeal fractures, are safe and reliable.