FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis.

N6-methyladenosine (m6A) modification is one of the most prevalent forms of epigenetic modification and plays an important role in the development of degenerative diseases such as osteoarthritis (OA). However, the evidence concerning the role of m6A modification in OA is insufficient. Here, m6A modification was increased in human OA cartilage and degenerated chondrocytes.

Restrained Mitf-associated autophagy by Mulberroside A ameliorates osteoclastogenesis and counteracts OVX-Induced osteoporosis in mice.

Bone and mineral metabolism homeostasis accounts for the maintenance of normal skeletal remodeling. However, with aging and changes in hormone levels, over-activated osteoclasts disrupt homeostasis, induce osteoporosis, and even cause osteoporotic fractures, leading to an enormous economic burden. Despite the rapid development of pharmacological therapy for osteoporosis, safer and more effective treatments remain to be explored.

Pexmetinib suppresses osteoclast formation and breast cancer induced osteolysis via P38/STAT3 signal pathway.

Breast cancer metastases to the bone can lead to a series of bone-related events that seriously affect the quality of life. Pexmetinib, a novel p38 mitogen-activated protein kinase (p38) inhibitor that has been evaluated in phase I clinical trials for myelodysplastic syndrome, but the effects of Pexmetinib on breast cancer induced osteolysis haven't been explored. Here, we found that Pexmetinib inhibited receptor activator of nuclear factor-κB ligand-induced osteoclast formation and bone resorption .

USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ.

Mutations and altered expression of deubiquitinating enzymes (DUBs) profoundly influence tumor progression. Ubiquitin-specific protease 1 (USP1) is a well-characterized human DUB reportedly overexpressed in and associated with maintaining the mesenchymal stem cell status of osteosarcoma (OS); however, the potential mechanisms of USP1 in OS remain poorly understood. In this study, we identified that USP1 directly interacts with Transcriptional Co-Activator With PDZ-Binding Motif (TAZ) in OS cell lines, and with mechanistic analysis indicating that the anti-OS effects of USP1 inhibition could be partially attributed to TAZ instability, with its reduced nuclear accumulation responsible for a subsequent decrease in the expression of downstream genes associated with the Hippo signaling pathway.

Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation.

Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density.

Correlation Analysis Between Basic Diseases and Subsequent Vertebral Fractures After Percutaneous Kyphoplasty (PKP) for Osteoporotic Vertebral Compression Fractures.

Background: Percutaneous kyphoplasty (PKP) is a widely accepted surgical treatment modality for painful osteoporotic vertebral compression fractures. The risk factors cause of subsequent vertebral fractures after PKP are debated.

Objectives: To evaluate risk factors for the occurrence of new vertebral compression fractures after PKP.

The SFRP1 Inhibitor WAY-316606 Attenuates Osteoclastogenesis Through Dual Modulation of Canonical Wnt Signaling.

Osteoporosis, a noteworthy age-related disease induced by imbalanced osteogenesis and osteoclastogenesis, is a serious economic burden on both individuals and society. Small molecule drugs with dual effects on both bone resorption and mineralization are pressingly needed. Secreted frizzled-related protein 1 (SFRP1), a well-known extracellular repressor of canonical Wnt signaling, has been reported to regulate osteogenesis.

Oxidative Stress-Induced Hypermethylation of KLF5 Promoter Mediated by DNMT3B Impairs Osteogenesis by Diminishing the Interaction with β-Catenin.

Emerging evidence suggests that the pathogenesis of osteoporosis, characterized by impaired osteogenesis, is shifting from estrogen centric to oxidative stress. Our previous studies have shown that the zinc-finger transcription factor krüppel-like factor 5 (KLF5) plays a key role in the degeneration of nucleus pulposus and cartilage. However, its role in osteoporosis remains unknown.

ML264 inhibits osteosarcoma growth and metastasis via inhibition of JAK2/STAT3 and WNT/β-catenin signalling pathways.

Osteosarcoma, the most common bone malignancy, has a high morbidity rate and poor prognosis. Krüppel-like factor 5 (KLF5) is a key transcriptional regulator of cellular proliferation whose overexpression is observed in osteosarcoma cell lines (U2OS, 143B, MG63 and SAOS2). ML264, a small-molecule inhibitor of KLF5, exerts antiproliferative effects in colorectal cancer; however, its function in osteosarcoma remains unknown.

The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice.

Background: Osteoclasts are key determinant cellular components implicated in the development and progression of disorders driven by bone damage. Herein, we studied the upshot of T007, an antagonist of peroxisome proliferator-activated receptor-gamma (PPARγ), on osteoclastogenesis using cell and animal models.

Results: The in vitro assays revealed that T007 hindered the osteoclastogenesis caused by the treatment with the receptor activator of nuclear factor-κB ligand (RANKL) through inhibiting the levels of PPARγ in cells.

The Nrf2 activator RTA-408 attenuates osteoclastogenesis by inhibiting STING dependent NF-κb signaling.

The dysregulation of ROS production and osteoclastogenesis is involved in the progress of osteoporosis. To identify novel and effective targets to treat this disease, it is important to explore the underlying mechanisms. In our study, we firstly tested the effect of the Nrf2 activator RTA-408, a novel synthetic triterpenoid under clinical investigation for many diseases, on osteoclastogenesis.

Administration of SB239063 Ameliorates Ovariectomy-Induced Bone Loss Suppressing Osteoclastogenesis in Mice.

Activation of osteoclast formation and function is crucial for the development of osteolytic diseases such as osteoporosis. RANKL (receptor activator of nuclear factor-κB ligand) activates NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase), and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1) signaling pathways to induce osteoclastogenesis. In this study, we demonstrated that SB239063, a p38-specific inhibitor, suppressed osteoclastogenesis and bone resorption inhibiting phosphorylation of MEF2C (myocyte enhancer factor 2C) and subsequently leading to MEF2C degradation by ubiquitination.

Lycorine Induces Apoptosis and G1 Phase Arrest Through ROS/p38 MAPK Signaling Pathway in Human Osteosarcoma Cells In Vitro and In Vivo.

Study Design: Xenograft osteosarcoma mouse model.

Objective: We determined the effect of lycorine on osteosarcoma.

Summary Of Background Data: Osteosarcoma is an aggressive malignant neoplasm, is most prevalent in teenagers and adults and current treatment approaches have reached a survival plateau and attempts to improve osteosarcoma prognosis have proven unsuccessful.

The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice.

Pamapimod (PAM) is a novel selective p38 mitogen-activated protein (MAP) kinase inhibitor proved to be effective in rheumatoid arthritis in phase 2 clinical trial. However, its effect on osteoclast-associated osteoporosis and the underlying mechanisms remain unclear. In this study, we showed that PAM suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via inhibition of p38 phosphorylation and subsequent c-Fos and nuclear factor of activated T cells c1 (NFATc1) expression.

Activating β-catenin/Pax6 axis negatively regulates osteoclastogenesis by selectively inhibiting phosphorylation of p38/MAPK.

Balance of osteoclast formation is regulated by the receptor activator of NF-κB ligand and extracellular negative regulators such as IFN-γ and IFN-β. However, very little is known about the intrinsic negative regulatory factors of osteoclast differentiation. Recently, the paired-box homeodomain transcription factor Pax6 was shown to negatively regulate receptor activator of NF-κB ligand-mediated osteoclast differentiation.

MicroRNA-543 promotes ovariectomy-induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2.

The present study aimed to determine the roles of miRNA-543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA-543 expression in osteoblasts was measured by quantitative real-time polymerase chain reaction.

Glabridin inhibits osteosarcoma migration and invasion via blocking the p38- and JNK-mediated CREB-AP1 complexes formation.

Osteosarcoma is the most common bone malignancy, and it seriously affects the quality of life of affected children and adolescents. Glabridin (GLA), a major component of licorice root extract, has been reported to exert antitumor effects against a variety of tumor types; however, its effects on osteosarcoma have not been elucidated. In the current study, we investigate the effects and potential antimetastatic mechanisms of GLA on osteosarcoma in vitro and in vivo.

Ascorbic Acid Attenuates Multifidus Muscles Injury and Atrophy After Posterior Lumbar Spine Surgery by Suppressing Inflammation and Oxidative Stress in a Rat Model.

Study Design: A rat model of multifidus muscles injury and atrophy after posterior lumbar spine surgery.

Objective: We determined the effect of ascorbic acid (AA) on the postoperative multifidus muscles in rat model.

Summary Of Background Data: Previous studies show oxidative stress and inflammation are two main molecular mechanisms in multifidus muscle injury and atrophy after posterior lumbar surgery.