Immunometabolism of macrophages in the bone microenvironment: a new perspective for bone healing therapy.

Background: Immunometabolism, the regulation of immune cell function through metabolic pathways, has emerged as a key focus in regenerative medicine. Traditional bone healing therapies primarily target the osteoblast-osteoclast regulatory axis, overlooking the metabolic reprogramming of immune cells (e.g.

Idebenone attenuates RANKL-induced osteoclastogenesis and improves bone mass in ovariectomized mice.

Postmenopausal osteoporosis (PMOP), driven by estrogen deficiency-induced osteoclast overactivation, poses a significant global health burden with limited therapeutic options. In this study, we investigated the potential of Idebenone (IDB) as a therapeutic agent for PMOP, focusing on its effects on osteoclast differentiation and underlying molecular mechanisms. Bone marrow-derived macrophages (BMMs) were cultured and stimulated to induce osteoclast differentiation, with or without IDB treatment.

Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect.

Causal Relationship Between Psychosocial Factors and Neck Pain: A Two-Sample Mendelian Randomization Study.

Purpose: Neck pain (NP) is a multifactorial disorder that leads to severe disability. This study aimed to investigate whether potential risk factors have a causal effect on NP at the genetic level using a two-sample Mendelian randomization (MR) analysis.

Methods: Summary-level data for potential risk factors, including distress, anxiety disorder, depression, mood, sleep disorder, loneliness, education, alcohol consumption, smoking, time spent using the computer, and physical activity, as well as NP, were obtained from multiple large-scale Genome-Wide Association Studies (GWAS).

Obstructive sleep apnea and osteoporosis: A bidirectional two-sample mendelian randomization analysis.

Background: Previous epidemiological studies have explored the association between obstructive sleep apnea (OSA) and osteoporosis (OP), with inconclusive results due to various biases. Herein, we sought to determine the causal association between OSA and OP through bidirectional two-sample Mendelian randomization analysis.

Methods: Summary-level data for OSA were acquired from the FinnGen consortium, while data for fractures and BMDs (FA-BMD, FN-BMD, LS-BMD and eBMD) were derived from the UKBB and GEFOS.

Catharanthine tartrate ameliorates osteoclastogenesis by destabilizing HIF-1α.

With the aging population, postmenopausal osteoporosis (PMOP), clinically manifested by reduced bone density, weakened skeletal strength, and compromised skeletal microstructure, has become the most prevalent type. The decline in estrogen levels fosters oxidative stress and osteoclastogenesis, which significantly enhance the activity of osteoclasts. Current treatments prefer to adopt relevant strategies to inactivate osteoclasts but come with unavoidable side effects.

Heme metabolism mediates RANKL-induced osteoclastogenesis via mitochondrial oxidative phosphorylation.

Bone undergoes life-long remodeling, in which disorders of bone remodeling could occur in many pathological conditions including osteoporosis. Understanding the cellular metabolism of osteoclasts (OCs) is key to developing new treatments for osteoporosis, a disease that affects over 200 million women worldwide per annum. We found that human OC differentiation from peripheral blood mononuclear cells derived from 8 female patients is featured with a distinct gene expression profile of mitochondrial biogenesis.

Macelignan Improves Functional Recovery After Spinal Cord Injury by Augmenting Autophagy via the AKT-mTOR-TFEB Signaling Pathway.

Spinal cord injury (SCI) presents considerable therapeutic challenges due to its complex pathophysiology, and effective treatments are currently lacking. Macelignan (Mace) has shown therapeutic effects in some neurological disorders, but its potential to enhance functional recovery in SCI and the underlying mechanisms are not well understood. This research endeavors to explore the therapeutic value of Mace in SCI and its underlying mechanism of action.

Activation of the Nrf2 Signaling Pathway by Tetrahydroberberine Suppresses Ferroptosis and Enhances Functional Recovery Following Spinal Cord Injury.

Recent research has identified ferroptosis, a newly recognized form of programmed cell death, is a crucial factor in spinal cord injury (SCI). Tetrahydroberberine (THB) is a tetrahydroisoquinoline alkaloid derived from the tuber of the poppy family plant, Corydalis, which is recognized for its antioxidant and neuroprotective properties. Despite these attributes, the potential protective effects of THB against SCI are yet to be thoroughly investigated.

A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects.

Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration.

Tetrahydroberberine Prevents Ovariectomy-Induced Bone Loss by Inhibiting RANKL-Induced Osteoclastogenesis and Promoting Osteoclast Apoptosis.

Postmenopausal osteoporosis (PMOP) arises from the disruption in bone remodeling caused by estrogen deficiency, leading to a heightened susceptibility to osteoporotic fractures in aging women. Tetrahydroberberine (THB) is a chemical compound extracted from , a member of the traditional Chinese medicine series "Zhejiang eight taste", possessing a variety of pharmacological functions such as lowering lipids and preventing muscle atrophy. However, the impact of THB on PMOP has not been systematically explored.

Lysosomal biogenesis and function in osteoclasts: a comprehensive review.

Lysosomes serve as catabolic centers and signaling hubs in cells, regulating a multitude of cellular processes such as intracellular environment homeostasis, macromolecule degradation, intracellular vesicle trafficking and autophagy. Alterations in lysosomal level and function are crucial for cellular adaptation to external stimuli, with lysosome dysfunction being implicated in the pathogenesis of numerous diseases. Osteoclasts (OCs), as multinucleated cells responsible for bone resorption and maintaining bone homeostasis, have a complex relationship with lysosomes that is not fully understood.

Inhibition of KIF11 ameliorates osteoclastogenesis via regulating mTORC1-mediated NF-κB signaling.

Osteoporosis, characterized by over-production and activation of osteoclasts, has become a major health problem especially in elderly women. In our study, we first tested the effect of Caudatin (Cau) in osteoclastogenesis, which is separated from Cynanchum auriculatum as a species of C-21 steroidal glyosides. The results indicated that Cau suppressed osteoclastogenesis in a time- and dose-dependent manner in vitro.

Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model.

Background: Osteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA.

Methods: We employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA.

[Regulatory function and mechanism of autophagy on osteoclast].

Osteoclast (OC) is multinucleated, bone-resorbing cells originated from monocyte/macrophage lineage of cells, excessive production and abnormal activation of which could lead to many bone metabolic diseases, such as osteoporosis, osteoarthritis, etc. Autophagy, as a highly conserved catabolic process in eukaryotic cells, which plays an important role in maintaining cell homeostasis, stress damage repair, proliferation and differentiation. Recent studies have found that autophagy was also involved in the regulation of osteoclast generation and bone resorption.

Alleviates Oxidative Stress-Induced Apoptosis and Cellular Dysfunction in Human Umbilical Vein Endothelial Cells /Heme Oxygenase-1 Pathway and Accelerates Wound Healing .

To explore the effect and mechanism of gastrodin (GAS) on human umbilical vein endothelial cells (HUVECs) apoptosis induced by oxidative stress and its function in wound healing. HUVECs were incubated with tert-butyl hydroperoxide (TBHP) to induce endothelial cell dysfunction and GAS was used as a protector. Cell viability was detected by Counting Kit-8 (CCK-8).

Sclareol prevents ovariectomy-induced bone loss in vivo and inhibits osteoclastogenesis in vitro via suppressing NF-κB and MAPK/ERK signaling pathways.

Postmenopausal osteoporosis (PMO) is a progressive disease occurring in elderly postmenopausal women that is characterized by low bone mass and impaired bone quality. Sclareol is a natural product (initially isolated from the leaves and flowers of Salvia Sclarea) that possesses immune-regulation and anti-inflammatory effects, but its role in osteoclastic formation and function as well as the PMO remains unknown. In the current study, we investigated the inhibitory effect of sclareol on osteoclastogenesis and progression of PMO.

Schisandrin B attenuates epidural fibrosis in postlaminectomy rats by inhibiting proliferation and extracellular matrix production of fibroblasts.

Laminectomy has been widely considered one of the most common treatments for lumbar disorders. Epidural fibrosis (EF) is a common complication after laminectomy, causing recurrent postoperative pain. Schisandrin B (Sch.