The Role and Interactive Mechanism of Endoplasmic Reticulum Stress and Ferroptosis in Musculoskeletal Disorders.

Endoplasmic reticulum (ER) stress is a cellular phenomenon that arises in response to the accumulation of misfolded proteins within the ER. This process triggers the activation of a signalling pathway known as the unfolded protein response (UPR), which aims to restore ER homeostasis by reducing protein synthesis, increasing protein degradation, and promoting proper protein folding. However, excessive ER stress can perturb regular cellular function and contribute to the development of diverse pathological conditions.

Deferoxamine alleviates chondrocyte senescence and osteoarthritis progression by maintaining iron homeostasis.

Background: Osteoarthritis (OA) is a prevalent age-related disease characterized by the gradual deterioration of cartilage. The involvement of chondrocyte senescence is crucial in the pathogenesis of OA. Desferoxamine (DFO) is an iron chelator with therapeutic potential in various diseases.

DMT1-mediated iron overload accelerates cartilage degeneration in Hemophilic Arthropathy through the mtDNA-cGAS-STING axis.

Introduction: Excess iron contributes to Hemophilic Arthropathy (HA) development. Divalent metal transporter 1 (DMT1) delivers iron into the cytoplasm, thus regulating iron homeostasis.

Objectives: We aimed to investigate whether DMT1-mediated iron homeostasis is involved in bleeding-induced cartilage degeneration and the molecular mechanisms underlying iron overload-induced chondrocyte damage.

The roles of the Hippo-YAP signalling pathway in Cartilage and Osteoarthritis.

Osteoarthritis (OA) is an age-related disease, characterized by cartilage degeneration. The pathogenesis of OA is complicated and the current therapeutic approaches for OA are limited. Cartilage, an integral part of the skeletal system composed of chondrocytes, is essential for skeletal development, tissue patterning, and maintaining the normal activity of joints.

Corrigendum: Deferoxamine alleviates osteoarthritis by inhibiting chondrocyte ferroptosis and activating the Nrf2 pathway.

[This corrects the article DOI: 10.3389/fphar.2022.

A novel implant surface modification mode of Fe3O4-containing TiO2 nanorods with sinusoidal electromagnetic field for osteoblastogenesis and angiogenesis.

Implants made of Ti and its alloys are widely utilized in orthopaedic surgeries. However, insufficient osseointegration of the implants often causes complications such as aseptic loosening. Our previous research discovered that disordered titanium dioxide nanorods (TNrs) had satisfactory antibacterial properties and biocompatibility, but TNrs harmed angiogenic differentiation, which might retarded the osseointegration process of the implants.

JNK-JUN-NCOA4 axis contributes to chondrocyte ferroptosis and aggravates osteoarthritis via ferritinophagy.

Interruption of iron homeostasis is correlated with cell ferroptosis and degenerative diseases. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy has been reported as a vital mechanism to control cellular iron levels, but its impact on osteoarthritis (OA) pathology and the underline mechanism are unknown. Herein we aimed to investigate the role and regulatory mechanism of NCOA4 in chondrocyte ferroptosis and OA pathogenesis.

Probucol suppresses osteoclastogenesis via activating Nrf2 signaling and ameliorates ovariectomy-induced bone loss.

Osteoporosis is a systemic and endocrine bone disorder distinguished by declined bone mineral density, compromised bone strength, and destruction of trabecular structure. The abnormally excessive osteoclastogenesis and bone erosion play imperative roles in the progression of osteoporosis. However, treatment of osteoporosis is far from satisfactory due to poor adherence to existing medications and adverse reactions, there is an urgent to develop novel therapies for osteoporosis.

Indirubin protects chondrocytes and alleviates OA by inhibiting the MAPK and NF-κB pathways.

Pharmacological Relevance: Indirubin (IR) is a key active ingredient in the traditional Chinese medication QingDai, also called indigo naturalis, which are extensively used in China to treat chronic diseases, such as inflammation and cancer. However, the function of IR in reducing chondrocyte inflammation in osteoarthritis (OA) is still unclear.

Aim Of The Study: The aim of this research was to examine how IR inhibits arthritis and to highlight some of its cellular-level processes.

Nonunion of humeral medial condyle fracture caused by excessive functional exercise: a case report and review of the literature.

Background: Medial epicondyle fractures are one of the more common humerus fractures, but humeral medial condyle fracture (HMCF) is rare. Nonunion of medial humeral condyle fractures due to functional exercise is less common.

Case Presentation: We report a 5-year-old patient with a nonunion HMCF due to excessive functional exercise, who bruised the elbow 1 year ago and had no positive findings on all imaging studies.

Nucleic acid direct delivery to fibroblasts: a review of nucleofection and applications.

The fibroblast is one of the ideal target cell candidates for cell-based gene therapy approaches to promote tissue repair. Gene delivery to fibroblasts by viral transfection has been confirmed to have high transfection efficiency. However, in addition to immunogenic effects of viruses, the random integration of viral genes may damage the genome, affect the cell phenotype or even cause cancerous mutations in the transfected cells.

Blocking the cytohesin-2/ARF1 axis by SecinH3 ameliorates osteoclast-induced bone loss via attenuating JNK-mediated IRE1 endoribonuclease activity.

cytohesin-2 is a guanine nucleotide exchange factor to activate ARF1 and ARF6, which are involved in various biological processes, including signal transduction, cell differentiation, cell structure organization, and survival. Nevertheless, there is a lack of evidence revealing the role of cytohesin-2 in osteoclast differentiation and in the development of osteoporosis. In this study, we find cytohesin-2 and ARF1 positively regulate osteoclast differentiation and function.

Skin grafting treatment of adolescent lower limb avulsion injury.

Background: Under the influence of various factors, the number of lower extremity avulsion injuries in adolescents is increasing year by year. The main modality of treatment is skin grafting. There are many types of skin grafting.

Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway.

Osteoarthritis (OA) is a common disease with a complex pathology including mechanical load, inflammation, and metabolic factors. Chondrocyte ferroptosis contributes to OA progression. Because iron deposition is a major pathological event in ferroptosis, deferoxamine (DFO), an effective iron chelator, has been used to inhibit ferroptosis in various degenerative disease models.

The role of Ca /Calcineurin/NFAT signalling pathway in osteoblastogenesis.

The bone remodelling process is closely related to bone health. Osteoblasts and osteoclasts participate in the bone remodelling process under the regulation of various factors inside and outside. Excessive activation of osteoclasts or lack of function of osteoblasts will cause occurrence and development of multiple bone-related diseases.

Diaphyseal and Metaphyseal Modeling Defects-Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia.

Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets.

Phalangeal Intra-Articular Osteochondroma Caused a Rare Clinodactyly Deformity in Children: Case Series and Literature Review.

Background: Various factors are discovered in the development of clinodactyly. The purpose of this retrospective study was to present a group of children with a rare clinodactyly deformity caused by phalangeal intra-articular osteochondroma and evaluate the efficacy of various treatment methods.

Methods: All child patients that were treated for finger problems in our center between Jan 2017 and Dec 2020 were reviewed.

PERK signaling pathway in bone metabolism: Friend or foe?

Osteoblasts and osteoclasts participate in the process of bone remodelling to meet the needs of normal growth and development or repair pathological damage. Endoplasmic reticulum stress (ER stress) can break the intracellular homeostasis of osteoclasts and osteoblasts, which is closely related to abnormal bone remodelling. The double-stranded RNA-dependent protein kinase (PKR)-like ER kinase (PERK) is a key transmembrane protein that regulates ER stress, and growing evidence suggests that the PERK pathway plays a crucial role in regulating bone metabolism under both physiological and pathological conditions.

Growth differentiation factor 5 in cartilage and osteoarthritis: A possible therapeutic candidate.

Growth differentiation factor 5 (GDF-5) is essential for cartilage development and homeostasis. The expression and function of GDF-5 are highly associated with the pathogenesis of osteoarthritis (OA). OA, characterized by progressive degeneration of joint, particularly in cartilage, causes severe social burden.

Chondrocyte ferroptosis contribute to the progression of osteoarthritis.

Background: Osteoarthritis (OA) is a complex process comprised of mechanical load, inflammation, and metabolic factors. It is still unknown that if chondrocytes undergo ferroptosis during OA and if ferroptosis contribute to the progression of OA.

Materials And Methods: In our study, we use Interleukin-1 Beta (IL-1β) to simulate inflammation and ferric ammonium citrate (FAC) to simulate the iron overload .

Hyperoside ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

Background: Osteoarthritis (OA) is a common degenerative joint disease. The pathogenesis of OA is closely related to inflammatory responses and apoptosis of chondrocytes. Hyperoside (Hyp), a natural flavonoid compound, exerts multiple bioactivities in various diseases.

PERK controls bone homeostasis through the regulation of osteoclast differentiation and function.

Osteoclasts are multinucleated giant cells with the ability to degrade bone tissue, and are closely related to abnormal bone metabolic diseases. Endoplasmic reticulum (ER) is an organelle responsible for protein modification, quality control, and transportation. The accumulation of unfolded or misfolded proteins in ER cavity induces ER stress.

Mitophagy in degenerative joint diseases.

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) and osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis and function is important. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, functions to maintain mitochondrial quality control and homeostasis.

PTEN inhibitor VO-OHpic attenuates GC-associated endothelial progenitor cell dysfunction and osteonecrosis of the femoral head via activating Nrf2 signaling and inhibiting mitochondrial apoptosis pathway.

Background: Glucocorticoid (GC)-associated osteonecrosis of the femoral head (ONFH) is the most common in non-traumatic ONFH. Despite a strong relationship between GC and ONFH, the detailed mechanisms have remained elusive. Recent studies have shown that GC could directly injure the blood vessels and reduce blood supply in the femoral head.