A5081077843- Cancer-related molecular mechanisms research
- Bone Metabolism and Diseases
- MicroRNA in disease regulation
- Immune cells in cancer
- Extracellular vesicles in disease
- Circular RNAs in diseases
- RNA Research and Splicing
- Dermatology and Skin Diseases
- RNA modifications and cancer
- Inflammatory mediators and NSAID effects
- Gut microbiota and health
- Circadian rhythm and melatonin
- Dietary Effects on Health
- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Kruppel-like factors research
- Bone and Joint Diseases
- Pain Mechanisms and Treatments
- Cytokine Signaling Pathways and Interactions
- Anesthesia and Pain Management
- Wnt/β-catenin signaling in development and cancer
- Spinal Hematomas and Complications
- Marine Ecology and Invasive Species
- Hedgehog Signaling Pathway Studies
Central South University
2014-2024
Xiangya Hospital Central South University
2017-2024
Northwest Women's and Children's Hospital
2021-2024
Zhengzhou University
2024
Army Medical University
2022
Endocrinology Research Center
2021-2022
Johns Hopkins University
2009-2020
Soil and Fertilizer Institute of Hunan Province
2018-2020
National Clinical Research Center for Digestive Diseases
2020
Johns Hopkins Medicine
2009-2019
Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce nerve axonal growth bone. Reduction osteoclast formation by knockout receptor activator nuclear factor kappa-B ligand (Rankl) osteocytes inhibited nerves into bone, dorsal root ganglion neuron hyperexcitability,...
Whether sensory nerve can sense bone density or metabolic activity to control homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in nerves regulate formation inhibiting sympathetic through the central nervous system. osteoblasts increases when decreases as demonstrated osteoporotic animal models. Ablation of erodes skeletal integrity. Specifically, knockout EP4 gene cyclooxygenase-2 (COX2) significantly reduces volume...
Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss adiposity. Here we identified a long noncoding RNA, Bmncr, regulated the fate of BMSCs during aging. Mice depleted Bmncr (Bmncr-KO) showed decreased mass increased adiposity, whereas transgenic overexpression (Bmncr-Tg) alleviated fat accumulation. niche by maintaining extracellular matrix protein fibromodulin (FMOD) activation BMP2 pathway....
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression the miR-497∼195 cluster high in endothelium but gradually decreases Mice with depletion endothelial cells fewer lower mass. Conversely, transgenic overexpression murine alleviates age-related reduction loss. maintains Notch activity HIF-1α stability via...
The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E2 (PGE2) secreted by osteoblasts could activate EP4 receptor to promote formation inhibiting sympathetic activity. However, the fundamental units are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found after denervation, knockout nerves, or COX-2 significantly adipogenesis and inhibit osteogenesis adult mice....
The accumulation and systemic propagation of senescent cells contributes to physiological aging age-related pathology. However, which cell types are most susceptible the aged milieu could be responsible for senescence has remained unclear. Here we found that physiologically bone marrow monocytes/macrophages (BMMs) propagate multiple tissues, through extracellular vesicles (EVs), drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a...
Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes SSPC remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during which triggers and impairs fracture healing. Local injection human rGCA young mice induced delayed repair. Genetic deletion Gca monocytes/macrophages was sufficient to rejuvenate repair aged alleviate senescence....
Osteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in osteocytes subchondral bone both spontaneous OA rheumatoid arthritis (RA). The knockout COX-2 or treatment with a inhibitor effectively rescues structure attenuates cartilage degeneration (STR/Ort) mice tumor necrosis factor-α transgenic RA mice. Thus, induces OA-associated...
High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in long noncoding RNA Reg1cp that associated with HBM. Subsequent analysis 1,465 Chinese subjects revealed heterozygous individuals had higher density compared WT Reg1cp. Mutant increased formation of CD31hiEmcnhi endothelium marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant directly binds to Krüppel-like factor 3...
Abstract Objectives Excessive oxidative stress and diminished antioxidant defences could contribute to age‐related tissue damage various diseases including osteoporosis. Dendrobium officinale polysaccharides (DOPs), a major ingredient from traditional Chinese medicine, have great potential of antioxidative activity. In this study, we explore the role DOP in osteoporosis that remains elusive. Materials methods Oxidative stimulation were used treat bone marrow mesenchymal stem cells (BMSCs),...
Abstract Objectives CD31 hi EMCN vessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for endomucin, couple angiogenesis osteogenesis. However, the role of in bone regeneration remains unknown. In present study, we investigated process regeneration. Materials Methods We used endothelial‐specific Krüppel like factor 3 ( Klf3 ) knockout mice ophiopogonin D treatment to interfere with vessel formation. constructed...
A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis osteogenesis recently. The number vessels in tissue declines age, the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves process. miRNA-188-3p upregulated skeletal endothelium negatively regulates formation during ageing. Mice depletion miR-188 showed an alleviated age-related decline vessels. In...
Abstract Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but functional role specific mechanisms P. IR remain unclear. In present study, clinical samples were analysed to determine statistical correlation between occurrence. Through culturing hepatocytes, myocytes, adipocytes, feeding mice orally, was further studied both vitro vivo. Clinical data...
Mechanical loading is required for bone homeostasis, but the underlying mechanism still unclear. Our previous studies revealed that mechanical protein polycystin-1 (PC1, encoded by Pkd1) critical formation. However, role of PC1 in resorption unknown. Here, we found directly regulates osteoclastogenesis and resorption. The conditional deletion Pkd1 osteoclast lineage resulted a reduced number osteoclasts, decreased resorption, increased mass. A cohort study 32,500 patients further autosomal...
Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue underlying mechanisms are still unclear. Here, we show that obesity triggers changes in microRNA profile macrophage-secreted extracellular vesicles, leading to a switch stem/progenitor (SSPC) differentiation between osteoblasts adipocytes bone deterioration. Bone marrow macrophage (BMM)-secreted vesicles (BMM-EVs) from obese mice...
Abstract Islet β cell dysfunction and insulin resistance are the main pathogenesis of type 2 diabetes (T2D), but mechanism remains unclear. Here we identify a rs3819316 C > T mutation in lncRNA Reg1cp mainly expressed islets associated with an increased risk T2D. Analyses 16,113 Chinese adults reveal that Mut-Reg1cp individuals had higher incidence T2D presented impaired secretion as well resistance. Mice islet specific knock-in have more severe Mass spectrometry assay proteins after RNA...