Manipulating PP2Acα-ASK-JNK signaling to favor apoptotic over necroptotic hepatocyte fate reduces the extent of necrosis and fibrosis upon acute liver injury.

In the widely used Carbon tetrachloride (CCl)-induced acute liver injury (ALI) mouse model, hepatocytes are known to die from programmed cell death (PCD) processes including apoptosis and necroptosis. Both in vivo and in vitro experiments showed that CCl treatment could induce both apoptosis and necroptosis. Treatment of mice with the apoptosis inducer SMAC mimetic reduced necroptosis, led to less pronounced liver damage, and improved overall liver function.

Heterogeneity analysis of astrocytes following spinal cord injury at single-cell resolution.

Astrocytes play many important functions in response to spinal cord injury (SCI) in an activated manner, including clearance of necrotic tissue, formation of protective barrier, maintenance of microenvironment balance, interaction with immune cells, and formation of the glial scar. More and more studies have shown that the astrocytes are heterogeneous, such as inflammatory astrocyte 1 (A1) and neuroprotective astrocyte 2 (A2) types. However, the subtypes of astrocyte resulting from SCI have not been clearly defined.

Effects of Mechanical Compression on Chondrogenesis of Human Synovium-Derived Mesenchymal Stem Cells in Agarose Hydrogel.

Mechanical compression is a double-edged sword for cartilage remodeling, and the effect of mechanical compression on chondrogenic differentiation still remains elusive to date. Herein, we investigate the effect of mechanical dynamic compression on the chondrogenic differentiation of human synovium-derived mesenchymal stem cells (SMSCs). To this aim, SMSCs encapsulated in agarose hydrogels were cultured in chondrogenic-induced medium with or without dynamic compression.

Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries.

Tendons and tendon interfaces have a very limited regenerative capacity, rendering their injuries clinically challenging to resolve. Tendons sense muscle-mediated load; however, our knowledge on how loading affects tendon structure and functional adaption remains fragmentary. Here, we provide evidence that the matricellular protein secreted protein acidic and rich in cysteine (SPARC) is critically involved in the mechanobiology of tendons and is required for tissue maturation, homeostasis, and enthesis development.

Serum levels of leptin, osteopontin, and sclerostin in patients with and without knee osteoarthritis.

Objective: To investigate the relationship between leptin, osteopontin (OPN), sclerostin (SOST) and severity of knee osteoarthritis (KOA).

Methods: The study included 148 consecutive patients with knee OA and 101 non-KOA subjects enrolled in this cross-sectional study. All patients fulfilled the American College of Rheumatology criteria for primary knee OA.

Application of robotic-assisted 3D printing in cartilage regeneration with HAMA hydrogel: An study.

The concept of 3D bio-printing was previously reported, while its realization has still encountered with several difficulties. The present study aimed to report robotic-assisted 3D bio-printing technology for cartilage regeneration, and explore its potential in clinical application. A six-degree-of-freedom (6-DOF) robot was introduced in this study, and a fast tool center point (TCP) calibration method was developed to improve printing accuracy.

Estrogen prevents articular cartilage destruction in a mouse model of AMPK deficiency via ERK-mTOR pathway.

Background: To investigate the mechanism underlying the chondroprotective effect of estrogen in AMP-activated protein kinase (AMPK) deficiency mice.

Methods: Female cartilage-specific AMPKα double knockout (AMPKα cDKO) mice were generated and subjected to ovariectomy (OVX). The model of osteoarthritis (OA) was induced by destabilization of medial meniscus (DMM).

Inhibition of pyroptosis attenuates -induced bone injury in traumatic osteomyelitis.

Background: Osteomyelitis is a severe bone infection and typically leads to progressive bone resorption, destruction and dysfunction. Pyroptosis is a form of programmed cell death involved in various infectious diseases. However, the identification of pyroptosis and the role it plays in osteomyelitis remains to be clarified.

Inactivation of in postnatal chondrocytes leads to epiphyseal growth-plate abnormalities and promotes enchondroma-like formation.

Liver serine-threonine kinase B1 (LKB1) is a tumor suppressor that has been linked to many types of tumors. However, the role of LKB1 in cartilaginous tumorigenesis is still poorly understood. In this study, we find that cartilage-specific, tamoxifen-inducible knockout results in multiple enchondroma-like lesions adjacent to the disorganized growth plates.

Recruitment of Brd3 and Brd4 to acetylated chromatin is essential for proinflammatory cytokine-induced matrix-degrading enzyme expression.

Background: Proinflammatory cytokines, which can upregulate the expression of matrix-degrading enzymes in chondrocytes, play important roles in the development of osteoarthritis. BET family proteins, acting as the "readers" of acetylated modifications on histones, have been linked to transcriptional regulation. And a BET protein inhibitor, I-BET151, has been shown to inhibit the induction of matrix-degrading enzymes by proinflammatory cytokines in chondrocytes.

A genome-wide association study identifies new genes associated with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is one of the most common congenital malformations and covers a spectrum of hip disorders from mild dysplasia to irreducible dislocation. The pathological mechanisms of DDH are poorly understood, which hampers the development of diagnostic tools and treatments. To gain insight into its disease mechanism, we explored the potential biological processes that underlie DDH by integrating pathway analysis tools and performing a genome-wide association study (GWAS).

The effectiveness of allogeneic mesenchymal stem cells therapy for knee osteoarthritis in pigs.

Background: Intraarticular injection of the mesenchymal stem cells (MSCs) has shown to be successful for treating osteoarthritis (OA). Nevertheless, many studies have been focusing on autologous MSCs. The following study investigates the safety and effectiveness of intraarticular injection of allogenic MSCs in a pig OA model.

Evaluation of a polyvinyl alcohol-alginate based hydrogel for precise 3D bioprinting.

In this study, we designed a polyvinyl alcohol (PVA)-alginate based hydrogel and evaluated its cytocompatibility and printability. The samples were fabricated by 3D printing using a freeze-thaw process. The scanning electron microscope, material testing machine, rheometer, and cell counting kit-8 assay were used to examine the morphology, mechanical properties, rheological properties, and cytocompatiblity of the scaffolds, respectively.

Egr1 deficiency disrupts dynamic equilibrium of chondrocyte extracellular matrix through PPARγ/RUNX2 signaling pathways.

Background: This study is to investigate the effect of Egr1 on the mineralization and accumulation of chondrocyte extracellular matrix.

Methods: The femoral heads of patients of various heights were collected. Egr1 knockout mice were used.

3D printing individualized heel cup for improving the self-reported pain of plantar fasciitis.

Background: To explore the therapeutic effect and the biomechanical mechanism of 3D printing individualized heel cup in treating of plantar heel pain.

Methods: The clinical effect was evaluated by plantar pressure analysis and pain assessment in participants. Its biomechanical mechanism of protecting the plantar heel was explored using finite element simulation.

High preoperative serum leptin level is an independent risk factor for deep vein thrombosis after total knee arthroplasty in osteoarthritis patients: A prospective and cross-sectional study.

It suggests that a high leptin level may increase the risk of venous thromboembolism (VTE) in animal studies. However, clinical studies in this field are still largely unexplored. Our objective was to evaluate the relationship between the preoperative serum leptin levels and postoperative VTE incidence in osteoarthritis (OA) patients who underwent total knee arthroplasty (TKA) at our institute.

Bi-directional regulation of cartilage metabolism by inhibiting BET proteins-analysis of the effect of I-BET151 on human chondrocytes and murine joints.

Background: Proinflammatory cytokines, which can upregulate the expression of matrix-degrading enzymes in chondrocytes, play important roles in the development of osteoarthritis. And a BET protein inhibitor, I-BET151, has been shown to exert an anti-inflammatory effect by repressing the BET protein-mediated expression of inflammatory genes. Our objective is to investigate the effect of I-BET151 on a surgical mouse model of osteoarthritis (OA) and human chondrocytes.

FTO variant is not associated with osteoarthritis in the Chinese Han population: replication study for a genome-wide association study identified risk loci.

Background: Osteoarthritis is the most prevalent form of arthritis worldwide and is the major cause of pain and loss of function in elderly people. A signal of the fat mass and obesity-associated (FTO) gene had been reported in a genome-wide association study of osteoarthritis. The FTO polymorphism (rs8044769) might exert its effect on osteoarthritis through obesity, because it was reported as a body mass index-associated single-nucleotide polymorphism.

Age-dependent variations of cancellous bone in response to ovariectomy in C57BL/6J mice.

The ovariectomized (OVX) mouse model has been widely accepted to be suitable for the study of postmenopausal osteoporosis. However, whether C57BL/6J mice, a commonly used genetic background mouse strain, is an appropriate model for postmenopausal osteoporosis remains controversial. The present study investigated the effect of the OVX model on alterations in bone density and microarchitecture in C57BL/6J female mice of different ages.

Zhuangguguanjie formulation protects articular cartilage from degeneration in joint instability-induced murine knee osteoarthritis.

Zhuangguguanjie formulation (ZG) can provide noticeable relief from joint pain in patients suffering from knee osteoarthritis (OA). However, the underlying mechanism has not been fully described. Male C57BL/6 mice were administered either ZG or normal saline (NS) following surgical destabilization of the medial meniscus (DMM).

Accelerated development of instability-induced osteoarthritis in transgenic mice overexpressing SOST.

Objective: Sclerostin (SOST), acting as a Wnt antagonist, has been shown to play a key role in regulating bone homestasis, and has also been linked to osteoarthritis (OA) development. Here, we investigated whether overexpressing SOST could affect OA development after destabilization of the medial meniscus (DMM) using mice.

Methods: Bone and cartilage phenotypes of mice at 10 weeks of age were investigated by dual x-ray absorptiometry (DXA) and histology.

Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model.

Background: This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model.

Methods: T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test.

A novel missense variant in is associated with developmental dysplasia of the hip in Han Chinese population.

Developmental dysplasia of the hip (DDH) is one of the most common inborn disabilities of the hip joint and a common disease with a genetic component for its etiology. However, genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. Previous study has identified that is significant associated with osteoarthritis and the development of chondrocytes and bone.

Changes in expression of Wnt signaling pathway inhibitors dickkopf-1 and sclerostin before and after total joint arthroplasty.

The aim is to study how serum concentration of Dickkopf-1 (DKK1) and Sclerostin (SOST) varies in patients before and after undergoing total joint arthroplasty (TJA). A total of 104 patients undergoing TJA were included in this study. Serum DKK1 and SOST were measured at 1 day before and 1, 3, and 5 days after surgery.

In situ repair of bone and cartilage defects using 3D scanning and 3D printing.

Three-dimensional (3D) printing is a rapidly emerging technology that promises to transform tissue engineering into a commercially successful biomedical industry. However, the use of robotic bioprinters alone is not sufficient for disease treatment. This study aimed to report the combined application of 3D scanning and 3D printing for treating bone and cartilage defects.