Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis.

Ferroptosis is a necrotic form of iron-dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density.

Regulating lithium extraction based on intercalated SO in Li/Al-LDHs.

Reasonable construction of Li/Al-LDHs with interlayer anions is essential to improve the adsorption performance, especially for intercalating SO anions and blocking Li desorption. Hence, anion exchange between Cl and SO in the interlayer of Li/Al-LDHs was designed and prepared to demonstrate the strong exchangeability of SO for Cl intercalated in the Li/Al-LDH interlayer. Intercalated SO enlarged the interlayer spacing and significantly transformed the stacking structure of Li/Al-LDHs, resulting in fluctuating adsorption performance with changes in the intercalated SO content at different ionic strengths.

Magnetically Guided Intracartilaginous Delivery of Kartogenin Improves Stem Cell-Targeted Degenerative Arthritis Therapy.

Background: Degenerative joint disease or osteoarthritis (OA) is a leading cause of disability worldwide. Intra-articular injection is the mainstay nonsurgical treatment for OA. However, dense cartilage and a lack of vasculature often limit the ability of drugs to reach cell or tissue targets at the concentrations necessary to elicit the desired biological response.

Berbamine inhibits RANKL- and M-CSF-mediated osteoclastogenesis and alleviates ovariectomy-induced bone loss.

Osteoporosis is a common public health problem characterized by decreased bone mass, increased bone brittleness and damage to the bone microstructure. Excessive bone resorption by osteoclasts is the main target of the currently used drugs or treatment for osteoporosis. Effective antiresorptive drugs without side effects following long-term administration have become a major focus of anti-osteoporotic drugs.

Immune checkpoint inhibitors in osteosarcoma: A hopeful and challenging future.

Osteosarcoma (OS), the most common malignant tumor in the musculoskeletal system, mainly occurs in adolescents. OS results in high mortality and disability rates due to a fatal metastatic tendency and subsequent iatrogenic damage caused by surgery, radiotherapy and chemotherapy. Recently, immunotherapies have resulted in promising prognoses with reduced side effects compared with traditional therapies.

Outcomes of Eight-Plate Epiphysiodesis for Residual Clubfoot Deformities.

Objective: The outcome of congenital clubfoot treatment is still challenging if the feet deformities are not completely corrected. Here we explore a minimal invasive procedure with an eight-plate implant to correct the residual forefoot adduction deformity after treatment of neglected or relapsed clubfoot.

Methods: We retrospectively reviewed patients with residual forefoot adduction deformity after clubfoot treatment between January 2013 and June 2016.

Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways and attenuates osteoarthritis .

Osteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects.

Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis.

Targeting cartilage is a promising strategy for the treatment of osteoarthritis, and various delivery vehicles were developed to assist the therapeutic agents into cartilage. However, the underlying biomechanisms and potential bioactivities remain oversimplified. Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β.

Hybrid Nanofibrous Composites with Anisotropic Mechanics and Architecture for Tendon/Ligament Repair and Regeneration.

Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility.

Acellular nerve grafts supplemented with induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery.

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability. Herein, we selected induced pluripotent stem cells (iPSCs) derived exosomes to supplement acellular nerve grafts (ANGs) with the aim of restoring long-distance peripheral nerve defects. Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4, Sox2, Klf4, and c-Myc.

Irrigation and debridement for knee osteoarthritis patients with suspected infection by intra-articular injection before total knee arthroplasty: a retrospective study.

Background: Patients suffer from knee osteoarthritis (KOA) pain may seek for intra-articular injections before total knee arthroplasty (TKA), which have a possibility of causing the joint sepsis. However, the management and clinical outcomes of these patients following TKA remain uncertain.

Methods: Patients with a history of intra-articular injection, in which a joint sepsis was suspected, were included.

Development and validation of a prediction model for glucocorticoid-associated osteonecrosis of the femoral head by targeted sequencing.

Objective: To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults.

Methods: This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People's Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks.

Engeletin Protects Against TNF-α-Induced Apoptosis and Reactive Oxygen Species Generation in Chondrocytes and Alleviates Osteoarthritis in vivo.

Purpose: Osteoarthritis (OA) is a progressive disease characterized by pain and impaired joint functions. Engeletin is a natural compound with anti-inflammatory and antioxidant effects on other diseases, but the effect of engeletin on OA has not been evaluated. This study aimed to elucidate the protective effect of engeletin on cartilage and the underlying mechanisms.

Reciprocal effect of microRNA-224 on osteogenesis and adipogenesis in steroid-induced osteonecrosis of the femoral head.

The adverse effects of glucocorticoids (GCs) on bone marrow stromal stem cells (BMSCs) play an important role in steroid-induced osteonecrosis of the femoral head (ONFH). Our previous miRNA microarray analysis indicated that microRNA-224-5p (miR-224-5p) could be a potential regulator; however, the underlying mechanism remains unclear. In the present study, we demonstrated that miR-224-5p was upregulated in GC-treated BMSCs, and functional experiments revealed that miR-224-5p could suppress osteogenic but promote adipogenic differentiation of BMSCs.

Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity.

Tumour cell phagocytosis by antigen presenting cells (APCs) is critical to the generation of antitumour immunity. However, cancer cells can evade phagocytosis by upregulating anti-phagocytosis molecule CD47. Here, we show that CD47 blockade alone is inefficient in stimulating glioma cell phagocytosis.

Serum Biomarkers Related to Glucocorticoid-Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case-Control Study.

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH.

Therapeutic Remodeling of the Tumor Microenvironment Enhances Nanoparticle Delivery.

A major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability.

The Reciprocity between Radiotherapy and Cancer Immunotherapy.

The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor.

Study of Osteocyte Behavior by High-Resolution Intravital Imaging Following Photo-Induced Ischemia.

Ischemic injuries and local hypoxia can result in osteocytes dysfunction and play a key role in the pathogenesis of avascular osteonecrosis. Conventional imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) can reveal structural and functional changes within bony anatomy; however, characterization of osteocyte behavioral dynamics in the setting of osteonecrosis at the single cell resolution is limited. Here, we demonstrate an optical approach to study real-time osteocyte functions in vivo.

Correction: The treatment of femoral neck fracture using VEGF-loaded nanographene coated internal fixation screws.

[This corrects the article DOI: 10.1371/journal.pone.

The treatment of femoral neck fracture using VEGF-loaded nanographene coated internal fixation screws.

Purpose: Previous studies have proved that vascular endothelial growth factor (VEGF) has a dual role in the promotion of new bone formation and blood vessel repair during fracture healing. However, how to introduce VEGF to a fracture site safely and effectively is still a challenge. This study aimed to prepare a VEGF-loaded nanographene coated internal fixation screw and to evaluate its effects in the treatment of femoral neck fracture.

Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy.

Tumour-targeted immunotherapy offers the unique advantage of specific tumouricidal effects with reduced immune-associated toxicity. However, existing platforms suffer from low potency, inability to generate long-term immune memory and decreased activities against tumour-cell subpopulations with low targeting receptor levels. Here we adopted a modular design approach that uses colloidal nanoparticles as substrates to create a multivalent bi-specific nanobioconjugate engager (mBiNE) to promote selective, immune-mediated eradication of cancer cells.

Lessons from immuno-oncology: a new era for cancer nanomedicine?

Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.

Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes.

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear.