N-acetylcarnosine attenuates age-associated declines in multi-organ systems to improve survival.

Histidine containing dipeptides (HCDs) such as N-acetylcarnosine are endogenous metabolites that are ergogenic and mitigate metabolic dysfunction. We previously demonstrated that short-term N-acetylcarnosine treatment is highly efficacious in protecting muscle atrophy induced by disuse. Here we demonstrate that a 6-months treatment of N-acetylcarnosine attenuates a broad spectrum of age-associated maladies and improved survival by ∼50% in female mice.

Divergent Requirements for Glutathione Biosynthesis During Osteoclast Differentiation In Vitro and In Vivo.

Glutathione (GSH) is the most abundant antioxidant in the cell, and it is responsible for neutralizing reactive oxygen species (ROS). ROS can promote osteoclast differentiation and stimulate bone resorption and are some of the primary drivers of bone loss with aging and loss of sex steroids. Despite this, the role of GSH biosynthesis during osteoclastogenesis remains controversial.

Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice.

Osteoclasts are bone resorbing cells that are essential to maintain skeletal integrity and function. While many of the growth factors and molecular signals that govern osteoclastogenesis are well studied, how the metabolome changes during osteoclastogenesis is unknown. Using a multifaceted approach, we identified a metabolomic signature of osteoclast differentiation consisting of increased amino acid and nucleotide metabolism.

sp. nov. and sp. nov., Pink-Pigmented Bacteria Isolated from Root Nodules of (Retz.) Poir.

Four pigment-producing rhizobial strains nodulating (Retz.) Poir. formed a unique group in genus in the phylogeny of a 16S rRNA gene and five housekeeping genes (, , , , and ) in a genome analysis, phenotypic characteristics analysis, and chemotaxonomic analysis.

Molecular mechanism of Rolupram reducing neuroinflammation in noise induced tinnitus mice through TLR4/NF kB/NLRP3 protein/caspase-1/IL-1 β signaling pathway.

Noisy tinnitus is a common auditory system disease characterized by persistent tinnitus symptoms. The TLR4/NF - κ B/NLRP3 signaling pathway plays an important role in neuroinflammatory response. Select 6 control and 6 noise exposed mice for transcriptome sequencing analysis in the hippocampus, conduct high-throughput data analysis, identify differentially expressed genes, and screen for pathways.

Proteolytic activation of fatty acid synthase signals pan-stress resolution.

Chronic stress and inflammation are both outcomes and major drivers of many human diseases. Sustained responsiveness despite mitigation suggests a failure to sense resolution of the stressor. Here we show that a proteolytic cleavage event of fatty acid synthase (FASN) activates a global cue for stress resolution in Caenorhabditis elegans.

Glutathione limits RUNX2 oxidation and degradation to regulate bone formation.

Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since elevated ROS has been shown to have deleterious effects on osteoblasts. Moreover, excessive ROS is thought to underlie many of the skeletal phenotypes associated with aging and sex steroid deficiency in mice and humans.

Bioenergetic Metabolism In Osteoblast Differentiation.

Purpose Of Review: Osteoblasts are responsible for bone matrix production during bone development and homeostasis. Much is known about the transcriptional regulation and signaling pathways governing osteoblast differentiation. However, less is known about how osteoblasts obtain or utilize nutrients to fulfill the energetic demands associated with osteoblast differentiation and bone matrix synthesis.

Obesity alters the collagen organization and mechanical properties of murine cartilage.

Osteoarthritis is a debilitating disease characterized by cartilage degradation and altered cartilage mechanical properties. Furthermore, it is well established that obesity is a primary risk factor for osteoarthritis. The purpose of this study was to investigate the influence of obesity on the mechanical properties of murine knee cartilage.

Tumor Necrosis Factor Receptor Associated Factor 3 Modulates Cartilage Degradation through Suppression of Interleukin 17 Signaling.

Interleukin 17A (IL-17A) is critical in the pathogenesis of autoimmune diseases through driving inflammatory cascades. However, the role of IL-17 in osteoarthritis (OA) is not well understood. Tumor necrosis factor-receptor-associated factor 3 (TRAF3) is a receptor proximal negative regulator of IL-17 signaling.

MiR-146a Deletion Protects From Bone Loss in OVX Mice by Suppressing RANKL/OPG and M-CSF in Bone Microenvironment.

MicroRNAs play important roles in osteoporosis and show great potential for diagnosis and therapy of osteoporosis. Previous studies have demonstrated that miR-146a affects osteoblast (OB) and osteoclast (OC) formation. However, these findings have yet to be identified in vivo, and it is unclear whether miR-146a is related to postmenopausal osteoporosis.

Overexpression of mechanical sensitive miR-337-3p alleviates ectopic ossification in rat tendinopathy model via targeting IRS1 and Nox4 of tendon-derived stem cells.

Tendinopathy, which is characterized by the ectopic ossification of tendon, is a common disease occurring in certain population, such as athletes that suffer from repetitive tendon strains. However, the molecular mechanism underlying the pathogenesis of tendinopathy caused by the overuse of tendon is still lacking. Here, we found that the mechanosensitive miRNA, miR-337-3p, had lower expression under uniaxial cyclical mechanical loading in tendon-derived stem cells (TDSCs) and negatively controlled chondro-osteogenic differentiation of TDSCs.

PIP5k1β controls bone homeostasis through modulating both osteoclast and osteoblast differentiation.

PIP5k1β is crucial to the generation of phosphotidylinosotol (4, 5)P2. PIP5k1β participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to examine the function of PIP5k1β in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment.

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.

Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, decreased bone mass, and in severe cases, osteoporosis. Glutamine metabolism has emerged as a critical regulator of many cellular processes in diverse pathologies.

TNF-α inhibits SATB2 expression and osteoblast differentiation through NF-κB and MAPK pathways.

Although the mechanisms of Tumor necrosis factor alpha (TNF-α) on facilitating osteoclast differentiation and bone resorption is well known, the mechanisms behind the suppression of the osteoblast differentiation from mesenchymal stem cells (MSCs) are still poorly understood. In this study, we observed a negative correlation between TNF-α levels and the expression of special AT-rich sequence-binding protein 2 (SATB2), a critical osteoblastogenesis transcription factor, in ovariectomy (OVX)-induced bone loss and IL-1-induced arthritis animal model. We found that TNF-α treatment inhibited mesenchymal cell line C2C12 osteoblast differentiation and sharply decreased BMP2-induced SATB2 expression.

Involvement of microRNA-23b in TNF-α-reduced BMSC osteogenic differentiation via targeting runx2.

Elucidation of the molecular mechanism governing bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation is of great importance for improving the treatment of osteoporosis. TNF-α is a well-known inhibitory factor during osteogenic differentiation of BMSCs. In our experiment, we consistently observed that TNF-α significantly inhibited BMSC osteogenic differentiation, which was partially rescued by BAY 11-7082 (NF-κB inhibitor).

MicroRNA-145 attenuates TNF-α-driven cartilage matrix degradation in osteoarthritis via direct suppression of MKK4.

Cartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and tumor necrosis factor (TNF)-α has critical role in this process by driving inflammatory cascades and cartilage degradation. However, the negative regulation of TNF-α-mediated signaling remains undefined. Here we demonstrate the crucial role of miR-145 in the modulation of TNF-α-mediated signaling and cartilage matrix degradation.

Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption .

Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms.

Anti-inflammatory and anti-osteoarthritis effects of tectorigenin.

Osteoarthritis (OA) is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear.

Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of Sonic Hedgehog.

Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro.

Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs).

KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of bone mesenchymal stem cells during osteoporosis.

Bone morphogenetic protein 2 (BMP2) has been used to induce bone regeneration by promoting osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). However, its effect is attenuated in osteoporotic conditions by unknown mechanisms. In this study, we investigated the molecular mechanisms of reduced osteogenic effect of BMP2 in osteoporotic conditions.

Gremlin2 Suppression Increases the BMP-2-Induced Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells Via the BMP-2/Smad/Runx2 Signaling Pathway.

Osteoblasts are essential for maintaining skeletal architecture and modulating bone microenvironment homeostasis. From numerous associated investigations, the BMP-2 pathway has been well-defined as a vital positive modulator of bone homeostasis. Gremlin2 (Grem2) is a bone morphogenetic protein (BMP) antagonists.

Structural and luminescence modulation in 8-hydroxyquinolinate-based coordination polymers by varying the dicarboxylic acid.

Two Zn(ii) and Cd(ii) coordination polymers [ZnL2·2DMF] (1) and [CdL(OAc)] (2) were first synthesized by treating a novel 2-substituted 8-hydroxyquinolinate ligand HL involving a pyridyl group with zinc or cadmium salts. Two dicarboxylic acid ligands (H2BDC = 1,4-benzenedicarboxylic acid; H2BPDC = 4,4'-biphenyldicarboxylic acid) are employed as secondary auxiliary ligands to perform a systematic study on the structural diversities in the M(ii)-quinolinate frameworks. By introducing two dicarboxylate anions in the reaction system, four new polymers [Zn2L2(BDC)] (3), [Zn3L2I2(BPDC)·2MeOH·8H2O] (4), [Cd2L2(BDC)] (5) and [Cd2L2(BPDC)·2MeOH·4H2O] (6) were obtained.