DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1–14 days) and thyroid hormone hypertrophic medium (T3, 15–28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs’ therapeutic effect on cartilage regeneration and hypertrophy suppression.     

Role of Scaffolds,Subchondral, Intra-Articular Injections of Fresh Autologous Bone Marrow Concentrate Regenerative Cells in Treating Human Knee Cartilage Lesions: Different Approaches and Different Results

The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review whether joint, subchondral bone, or/and scaffolds implantation of fresh autologous bone marrow aspirate concentrated (BMAC) containing mesenchymal stem cells (MSCs) would improve osteoarthritis (OA). There is in vivo evidence that suggests that all these different approaches (intra-articular injections, subchondral implantation, scaffolds loaded with BMAC) can improve the patient. This review analyzes the evidence for each different approach to treat OA. We found that the use of intra-articular injections resulted in a significant relief of pain symptoms in the short term and was maintained in 12 months. However, the clinical trials indicate that the application of autologous bone marrow concentrates in combination with scaffolds or in injection in the subchondral bone was superior to intra-articular injection for long-term results. The tendency of MSCs to differentiate into fibrocartilage affecting the outcome was a common issue faced by all the studies when biopsies were performed, except for scaffolds implantation in which some hyaline cartilage was found. The review suggests also that both implantation of subchondral BMAC and scaffolds loaded with BMAC could reduce the need for further surgery.     

Vibrational Spectroscopy in Assessment of Early Osteoarthritis—A Narrative Review

Osteoarthritis (OA) is a degenerative disease, and there is currently no effective medicine to cure it. Early prevention and treatment can effectively reduce the pain of OA patients and save costs. Therefore, it is necessary to diagnose OA at an early stage. There are various diagnostic methods for OA, but the methods applied to early diagnosis are limited. Ordinary optical diagnosis is confined to the surface, while laboratory tests, such as rheumatoid factor inspection and physical arthritis checks, are too trivial or time-consuming. Evidently, there is an urgent need to develop a rapid nondestructive detection method for the early diagnosis of OA. Vibrational spectroscopy is a rapid and nondestructive technique that has attracted much attention. In this review, near-infrared (NIR), infrared, (IR) and Raman spectroscopy were introduced to show their potential in early OA diagnosis. The basic principles were discussed first, and then the research progress to date was discussed, as well as its limitations and the direction of development. Finally, all methods were compared, and vibrational spectroscopy was demonstrated that it could be used as a promising tool for early OA diagnosis. This review provides theoretical support for the application and development of vibrational spectroscopy technology in OA diagnosis, providing a new strategy for the nondestructive and rapid diagnosis of arthritis and promoting the development and clinical application of a component-based molecular spectrum detection technology.     

Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.     

配置500 MPa纵筋钢筋混凝土框架顶层端节点抗震性能试验研究

按照《混凝土结构设计规范》(GB 50010—2010)设计了6个配置500 MPa纵筋的钢筋混凝土框架顶层端节点,并进行了低周反复加载抗震性能试验,验证了规范规定的抗震措施对配置500 MPa钢筋的顶层端节点的有效性,分析了配置500 MPa级钢筋的顶层端节点的受力特点、节点区的破坏形态以及节点的综合抗震性能,并与受力条件基本相同的配置HRB335级纵筋节点的受力性能进行了对比,对采用不同延性指标评价配置不同强度钢筋节点的延性性能差异进行了讨论。     

Design and control of a planar bipedal robot ERNIE with parallel knee compliance

This paper presents the development of the planar bipedal robot ERNIE as well as numerical and experimental studies of the influence of parallel knee joint compliance on the energetic efficiency of walking in ERNIE. ERNIE has 5 links—a torso, two femurs and two tibias—and is configured to walk on a treadmill so that it can walk indefinitely in a confined space. Springs can be attached across the knee joints in parallel with the knee actuators. The hybrid zero dynamics framework serves as the basis for control of ERNIE’s walking. In the investigation of the effects of compliance on the energetic efficiency of walking, four cases were studied: one without springs and three with springs of different stiffnesses and preloads. It was found that for low-speed walking, the addition of soft springs may be used to increase energetic efficiency, while stiffer springs decrease the energetic efficiency. For high-speed walking, the addition of either soft or stiff springs increases the energetic efficiency of walking, while stiffer springs improve the energetic efficiency more than do softer springs. Electronic Supplementary Material  The online version of this article () contains supplementary material, which is available to authorized users.

虚拟膝关节镜手术中保持单元质量的体网格形变方法

在虚拟膝关节手术中,需要对膝关节进行大范围形变的实时模拟。本文针对四面体网格的膝关节模型,提出了采用LSD度量建立形变能量,然后将带约束的最优化问题转化为不带约束的最优化问题,最后通过带Armijo线性查找的非精确牛顿法求解最优化问题。在求解过程中,通过预估未知点的位置,减少迭代步数,提高了算法的效率。这种方法具有较好的保体积性,同时保证形变后的四面体网格不出现体元翻转和退化。该方法也能推广应用于其它类似的关节弯曲运动的变形中。     

Motion study of the hip joint in extreme postures

Many causes can be at the origin of hip osteoarthritis (e.g., cam/pincer impingements), but the exact pathogenesis for idiopathic osteoarthritis has not yet been clearly delineated. The aim of the present work is to analyze the consequences of repetitive extreme hip motion on the labrum cartilage. Our hypothesis is that extreme movements can induce excessive labral deformations and lead to early arthritis. To verify this hypothesis, an optical motion capture system is used to estimate the kinematics of patient-specific hip joint, while soft tissue artifacts are reduced with an effective correction method. Subsequently, a physical simulation system is used during motion to compute accurate labral deformations and to assess the global pressure of the labrum, as well as any local pressure excess that may be physiologically damageable. Results show that peak contact pressures occur at extreme hip flexion/abduction and that the pressure distribution corresponds with radiologically observed damage zones in the labrum.

Biologically inspired design of a parallel actuated humanoid robot

This paper presents the comparison for the role of bi-articular and mono-articular actuators in human and bipedal robot legs, in particular the hip and knee joint, for driving the design of a humanoid robot with inspirations from the biological system. The various constraints driving the design of both systems are also compared. Additional factors particular to robotic system are identified and incorporated in the design process. To do this, a dynamic simulation is used to determine loading conditions and the forces and power produced by each actuator under various arrangements. It is shown that while the design principles of humans and humanoids are similar, other constraints ensure that robots are still merely inspired by humans, and not direct copies. A simple design methodology that captures the complexity and constraints of such a system in this paper is proposed. Finally, a full-size humanoid robot that demonstrates the newfound principle is highlighted.