GLI1 Deficiency Impairs the Tendon-Bone Healing after Anterior Cruciate Ligament Reconstruction: In Vivo Study Using -Transgenic Mice.

Hedgehog (Hh) signaling plays a fundamental role in the enthesis formation process and GLI-Kruppel family member GLI1 () is a key downstream mediator. However, the role of in tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is unknown. To evaluate the tendon-bone healing after ACLR in (GLI1-NULL) mice, and compare (GLI1-HET) and wild type (WT) mice, a total of 45 mice, 15 mice each of GLI1-NULL, GLI1-HET and WT were used in this study.

Distinct Inflammatory Macrophage Populations Sequentially Infiltrate Bone-to-Tendon Interface Tissue After Anterior Cruciate Ligament (ACL) Reconstruction Surgery in Mice.

Macrophages are important for repair of injured tissues, but their role in healing after surgical repair of musculoskeletal tissues is not well understood. We used single-cell RNA sequencing (RNA-seq), flow cytometry, and transcriptomics to characterize functional phenotypes of macrophages in a mouse anterior cruciate ligament reconstruction (ACLR) model that involves bone injury followed by a healing phase of bone and fibrovascular interface tissue formation that results in bone-to-tendon attachment. We identified a novel "surgery-induced" highly inflammatory CD9+ IL1+ macrophage population that expresses neutrophil-related genes, peaks 1 day after surgery, and slowly resolves while transitioning to a more homeostatic phenotype.

Evaluation of sex differences in rodent anterior cruciate ligament injury.

The relative contributions of sex differences in anatomy, biomechanics, and hormones to the increased risk of anterior cruciate ligament (ACL) injury in female athletes remains unknown. The purpose of this study is to investigate sex differences in anatomy and biomechanics of the native and reconstructed ACL using our established murine model. A total of 140 12-week-old wild-type C57Bl/6 (70 male vs.

Ferrostatin-1 alleviates cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis.

Cobalt is the main component of metal prostheses in hip arthroplasty. Studies have shown that metal particles mainly composed of cobalt nanoparticles (CoNPs) can cause systemic and local toxic reactions due to various physical and chemical factors. Therefore, elucidating the underlying mechanisms of metal prosthesis action, coupled with identification of effective detoxification drugs are imperative to minimizing postoperative complications and prolonging the service life of these clinical tools.

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis.

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC-derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM-MSCs) in alleviating OA.

Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) can differentiate into all blood lineages to maintain hematopoiesis, wound healing, and immune functions. Recently, cobalt-chromium alloy casting implants have been used extensively in total hip replacements; however, cobalt nanoparticles (CoNPs) released from the alloy were toxic to HSCs and HPCs. We aimed to investigate the mechanism underlying the toxic effect of CoNPs on HSCs/HPCs and to determine the protective effect of selenomethionine (SeMet) against CoNPs and .

Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression analysis.

Background: Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA.

A paradox: Fe2+-containing agents decreased ROS and apoptosis induced by CoNPs in vascular endothelial cells by inhibiting HIF-1α.

Cobalt nanoparticles (CoNPs) released from hip joint implants are known to have a toxic effect on several organs probably through increasing reactive oxygen species (ROS). Ferrous ion (Fe2+) is well-known to enhance oxidative stress by catalysing the production of ROS. However, in our pilot study, we found that Fe2+ conversely inhibited the ROS production induced by CoNPs.

Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death.

As a main element in the hard metal industry, cobalt is one of the major components of human metal implants. Cobalt-containing implants, especially joint prostheses used for artificial joint replacement, can be corroded due to the complex physiological environment in vivo, producing a large number of nanoscale cobalt particles (Cobalt Nanoparticles, CoNPs). These CoNPs can be first accumulated around the implant to cause adverse local reactions and then enter into the blood vessels followed by reaching the liver, heart, brain, kidney, and other organs through systematic circulation, which leads to multi-system toxicity symptoms.

Supplementation with Fe2+-containing agents mitigated the toxic effect of CoNPs in vascular endothelial cells by inhibiting activation of hypoxia-inducible factor.

Cobalt nanoparticles (CoNPs) released from hip joint implants are known to have a toxic effect on several organs. The aim of this study was to examine the effects of CoNP toxicity on vascular endothelium and to elucidate the underlying mechanisms. Moreover, the role of three ferrous ion (Fe2+)containing agents in conferring resistance to the effects of CoNPs was investigated.

Bone Material Properties of Human Phalanges Using Vickers Indentation.

Objective: To investigate the microhardness distribution throughout the human hand phalanges using the Vickers method, which can be used to directly evaluate the bone mechanical properties at tissue level and provide an alternative means to investigate bone quality.

Methods: The phalanges bones involved in this study were collected from three healthy donors; fresh-frozen right limbs were used. The phalanges bones were dissected and cut into 3-mm thick slices perpendicular to the long axis in the phalanges base, the phalanges shaft, and the phalanges head with a low-speed saw and then the slices were polished with sandpaper.

Profiling lncRNA alterations during TNF‑α induced osteogenic differentiation of dental pulp stem cells.

The multipotent and easily accessible characteristics of dental pulp stem cells (DPSCs) make them a promising target for bone tissue engineering. Long non‑coding RNAs (lncRNAs) have an important role in the osteogenic differentiation of mesenchymal stem cells. Nevertheless, whether lncRNAs are involved in the osteogenic differentiation of DPSCs remains unclear.

MicroRNA-21-5p are involved in apoptosis and invasion of fibroblast-like synoviocytes through PTEN/PI3K/AKT signal.

The function of microRNA-21-5p (miR-21) in fibroblast-like synoviocytes in RA was still unclear. In our study, we used tumor necrosis factor alpha (TNFα) (10 ng/ml) to mimic RA-FLSs and we found that normal FLS stimulated with TNFα caused the increasing expression of miR-21, a disintegrin and metalloproteinase with thrombospondin motifs 5 and matrix metalloproteinase 3, which were in accord with RA-FLSs changes. Our data showed that miR-21 overexpression significantly increased cell invasion and decreased apoptosis in FLSs.

A prospective comparative study of hip resurfacing arthroplasty and large-diameter head metal-on-metal total hip arthroplasty in younger patients-a minimum of five year follow-up.

Introduction: Both hip resurfacing arthroplasty (HRA) and large-diameter head metal-on-metal total hip arthroplasty (LDH MoM THA) are generally used for young and active patients. A number of comparative studies of HRA and total hip arthroplasty have been published in the literature. However, studies that have compared HRA with LDH MoM THA are rare.

α-Tocopherol protected against cobalt nanoparticles and cocl induced cytotoxicity and inflammation in Balb/3T3 cells.

Context: Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.

Objective: We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.

Melatonin counteracts cobalt nanoparticle‑induced cytotoxicity and genotoxicity by deactivating reactive oxygen species‑dependent mechanisms in the NRK cell line.

Cobalt nanoparticles (CoNPs) released from metal‑on‑metal implants have caused considerable concern. Oxidative stress is associated with the mechanism underlying cobalt‑induced cytotoxicity and genotoxicity. The indolamine melatonin exhibits protective effects against damage induced by metals.

Endoplasmic reticulum stress participates in the progress of senescence and apoptosis of osteoarthritis chondrocytes.

Endoplasmic reticulum stress (ERS) has been shown to participate in many disease pathologies. Recent reports have reported that ERS exists in human osteoarthritis (OA) chondrocytes. During OA, chondrocytes exhibit increased level of some senescence marker, such as senescence-associated β-galactosidase (SA β-gal) activity.

Protective effects of Zn against cobalt nanoparticles and cobalt chloride-induced cytotoxicity of RAW 264.7cells via ROS pathway.

Recent concerns have emerged surrounding the toxicity that cobalt may represent when used in MOM implants. Owing to corrosion and wear of MOM implants, the subsequent released cobalt nanoparticles (CoNPs) or Co ions (Co) can cause adverse reactions, such as the generation of pseudotumors, extensive necrosis, early osteolysis, and implants failure. The present study confirmed that CoNPs and Co can induce dose- and time-dependent cytotoxicity with increasing reactive oxygen species (ROS) levels.

N-acetylcysteine Attenuates Cobalt Nanoparticle-Induced Cytotoxic Effects through Inhibition of Cell Death, Reactive Oxygen Species-related Signaling and Cytokines Expression.

Objective: Complex cobalt-chromium alloys, bearing surfaces of the second-generation metal-on-metal (MoM) hip prostheses, are subject to wear and generate cobalt nanoparticles (CoNPs). CoNPs could reduce cellular viability, activate the mitogen-activated protein kinase (MAPK) pathway and increase cell apoptosis via reactive oxygen species (ROS). However, the detailed mechanisms of ROS functioning on CoNP-mediated signaling molecules and cytotoxicity has not yet been fully demonstrated.

L-Ascorbic Acid Protected Against Extrinsic and Intrinsic Apoptosis Induced by Cobalt Nanoparticles Through ROS Attenuation.

Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co) are the most serious syndrome in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it. The purpose of this study was to explore the mechanism of this damage and to demonstrate if L-ascorbic acid (L-AA) could protect against the cell toxicities induced by CoNPs and Co in vitro.

Transcriptome changes during TNF-α promoted osteogenic differentiation of dental pulp stem cells (DPSCs).

Dental pulp stem cells (DPSCs), due to the ease of isolation and their capacities of multi-lineage differentiation, are considered as attractive resources for regenerative medicine. In a previous study, we showed that TNF-α promoted the osteogenic differentiation of DPSCs via the NF-κB signaling pathway. However, the mechanisms of such differentiation were largely unknown.

Prevention of Surgical Site Infection After Ankle Surgery Using Vacuum-Assisted Closure Therapy in High-Risk Patients With Diabetes.

Patients with diabetes have a high risk of surgical site infection (SSI) after ankle surgery. The aim of the present study was to investigate the efficacy of vacuum-assisted closure (VAC) in the prevention of SSI after ankle surgery compared with the efficacy of standard moist wound care (SMWC). A retrospective study was performed of unstable ankle fractures for surgical fixation in patients with diabetes from January 2012 to December 2014.

Gender differences of venous thromboembolism risk after total hip and total knee arthroplasty: a meta-analysis.

We performed a meta-analysis to evaluate gender differences of venous thromboembolism (VTE) risk after total hip (THA) and total knee arthroplasty (TKA). We searched PubMed and Web of Knowledge from their beginning to 25 July 2015. Pooled odds ratio (OR) and 95 % confidence interval (CI) for VTE risk were calculated.