Search

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. As is well known, ferroptosis is a kind of programmed cell death characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS), resulting in oxidative harm to cellular structures. In recent years, there has been increasing evidence indicating that ferroptosis occurs in musculoskeletal disorders (MSDs), with emerging recognition of the complex relationship between ER stress and ferroptosis. This review presents a summary of ER stress and the ferroptosis pathway. Most importantly, it delves into the significance of ER stress in the ferroptosis process within diverse skeletal or muscle cell types. Furthermore, we highlight the potential benefits of targeting the correlation between ER stress and ferroptosis in treating degenerative MSDs. [ABSTRACT FROM AUTHOR]

In order to investigate the recycling technology for efficiently recovering low-temperature wastewater waste heat from industrial production, we built an experimental device for forced boiling heat transfer in an annular tube. This paper takes a ring casing evaporator with an inner tube diameter of 30 mm, a length of 1450 mm, a wall thickness of 0.8 mm, and an outer tube diameter of 14.2 mm, which was used as the main object of study. We conducted experimental research on heat transfer in single-phase liquid flow and two-phase boiling phase change within annular tubes by varying the inlet circulating hot water temperature (60–85 °C), the mass flow rate of the circulating mass (0.85, 1.27, 1.69 kg m−2 s−1), and the inclination angle (0°–90°). The research results indicate that the heat transfer coefficient of boiling phase change within annular sleeves is significantly enhanced compared to convective heat transfer of single-phase liquid flow within annular tubes. This signifies that employing heat pipe technology for waste heat recovery can achieve highly efficient heat transfer processes. This study also reveals that with an increase in the inclination angle, the heat transfer coefficient on the boiling surface follows a trend of initial increase followed by a decrease. Near an inclination angle of 30° within the annular jacket tube, the heat transfer coefficient of two-phase boiling phase change reaches its maximum value. The findings of this study provide certain theoretical guidance for the application of heat pipe energy-saving technology in the field of medium- and low-temperature waste water recovery and utilization. [ABSTRACT FROM AUTHOR]

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. Ca2+/Calcineurin/NFAT signalling pathway regulates the growth and development of many types of cells, such as cardiomyocyte differentiation, angiogenesis, chondrogenesis, myogenesis, bone development and regeneration, etc. Some evidences indicate that this signalling pathway plays an extremely important role in bone formation and bone pathophysiologic changes. This review discusses the role of Ca2+/Calcineurin/NFAT signalling pathway in the process of osteogenic differentiation, as well as the influence of regulating each component in this signalling pathway on the differentiation and function of osteoblasts, whereby the relationship between Ca2+/Calcineurin/NFAT signalling pathway and osteoblastogenesis could be deeper understood. [ABSTRACT FROM AUTHOR]

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. IVDD and OA are similar joint diseases involving the degradation of cartilaginous tissues that are mainly caused by oxidative stress, cell apoptosis and extracellular matrix (ECM) degradation. Over the past decade, accumulating evidence indicates the essential role of mitophagy in the pathogenesis of IVDD and OA. Importantly, strategies by the regulation of mitophagy exert beneficial effects in the pre-clinical experiments. Given the importance and novelty of mitophagy, we provide an overview of mitophagy pathways and discuss the roles of mitophagy in IVDD and OA. We also highlight the potential of targeting mitophagy for the treatment of degenerative joint diseases. Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy and beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CDH6: cadherin 6; CEP: cartilaginous endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: extracellular matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin 1 beta; IMM: inner mitochondrial membranes; IVDD: intervertebral disc degeneration; MAPK8/JNK: mitogen-activated protein kinase 8; MFN1: mitofusin 1; MFN2: mitofusin 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: mitochondrial transmembrane potential; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NFE2L2: nuclear factor: erythroid 2 like 2; NP: nucleus pulposus; OA: osteoarthritis; OPA1: OPA1: mitochondrial dynamin like GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin protein ligase; PD: Parkinson disease; PGAM5: PGAM family member 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator 1 alpha; PHF23: PHD finger protein 23; PINK1: PTEN induced putative kinase 1; ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin 1; SIRT2: sirtuin 2; SIRT3: sirtuin 3; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a complicated degenerative disease that affects whole joint tissue. Currently, apart from surgical approaches to treat late stage OA, effective treatments to reverse OA are not available. Thus, the mechanisms leading to OA, and more effective approaches to treat OA should be investigated. According to available evidence, the PI3K/AKT/mTOR signaling pathway is essential for normal metabolism of joint tissues, but is also involved in development of OA. To provide a wide viewpoint to roles of PI3K/AKT/mTOR signaling pathway in osteoarthritis, a comprehensive literature search was performed using PubMed terms 'PI3K OR AKT OR mTOR' and 'osteoarthritis'. This review highlights the role of PI3K/AKT/mTOR signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation, and discusses how this signaling pathway affects development of the disease. We also summarize recent evidences of therapeutic approaches to treat OA by targeting the PI3K/AKT/mTOR pathway, and discuss potential challenges in developing these strategies for clinical treatment of OA. [ABSTRACT FROM AUTHOR]

Iron overload is common in patients with diseases such as hemoglobinopathies, hereditary hemochromatosis or elderly men and postmenopausal women. This disorder is frequently associated with bone loss and recently has been considered as an independent risk factor for osteoporosis. By excess reactive oxygen species (ROS) production through Fenton reaction, iron could induce osteoblast apoptosis, inhibit osteoblast osteogenic differentiation. Moreover, Iron could also promote osteoclasts differentiation and bone absorption. The goal of the study is to investigate whether icariin could reverse iron overload‐induced bone loss in vitro and in vivo. Icariin is the major active ingredient of Herba Epimedii and has antioxidant, antiosteoporosis functions. In the current study, we demonstrated that oral administration of icariin significantly prevented bone loss in iron overloaded mice. Icariin could protect against iron overload‐induced mitochondrial membrane potential dysfunction and ROS production, promote osteoblast survival and reverse the reduction of Runx2, alkaline phosphatase, and osteopontin expression induced by iron overload. Icariin also inhibited osteoclasts differentiation and function. Moreover, we also found that icariin remarkably reduced iron accumulation in bone marrow, suggesting that icariin has the ability to regulate systemic iron metabolism in vivo. These results indicated that icariin could be a potential natural resource for developing medicines to prevent or treat iron overload‐induced osteoporosis. Icariin could protect against iron overload‐induced mitochondrial membrane potential dysfunction and reactive oxygen species production, promote osteoblast survival and reverse the reduction of Runx2, alkaline phosphatase, and osteopontin expression induced by iron overload. Icariin also inhibited osteoclasts differentiation and function and iron accumulation in bone marrow. [ABSTRACT FROM AUTHOR]

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 in vitro . Also, we used the surgery-induced destabilized medial meniscus (DMM) mouse model to induce OA in vivo . We verify ferroptosis by its definition that defined by the Nomenclature Committee on Cell Death with both in vitro and in vivo model., Results: We observed that both IL-1β and FAC induced reactive oxygen species (ROS), and lipid ROS accumulation and ferroptosis related protein expression changes in chondrocytes. Ferrostatin-1, a ferroptosis specific inhibitor, attenuated the cytotoxicity, ROS and lipid-ROS accumulation and ferroptosis related protein expression changes induced by IL-1β and FAC and facilitated the activation of Nrf2 antioxidant system. Moreover, erastin, the most classic inducer of ferroptosis, promoted matrix metalloproteinase 13 (MMP13) expression while inhibited type II collagen (collagen II) expression in chondrocytes. At last, we proved that intraarticular injection of ferrostatin-1 rescued the collagen II expression and attenuated the cartilage degradation and OA progression in mice OA model., Conclusions: In summary, our study firstly proved that chondrocytes underwent ferroptosis under inflammation and iron overload condition. Induction of ferroptosis caused increased MMP13 expression and decreased collagen II expression in chondrocytes. Furthermore, inhibition of ferroptosis, by intraarticular injection of ferrostatin-1, in our case, seems to be a novel and promising option for the prevention of OA., The Translational Potential of This Article: The translation potential of this article is that we first indicated that chondrocyte ferroptosis contribute to the progression of osteoarthritis which provides a novel strategy in the prevention of OA., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 The Author(s).)