A5011800181- Osteoarthritis Treatment and Mechanisms
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Bone Metabolism and Diseases
- Musculoskeletal pain and rehabilitation
- Pregnancy-related medical research
- Bone and Joint Diseases
- Spine and Intervertebral Disc Pathology
- Erythrocyte Function and Pathophysiology
- Gut microbiota and health
- Mycobacterium research and diagnosis
- Advanced biosensing and bioanalysis techniques
- Rheumatoid Arthritis Research and Therapies
- Circular RNAs in diseases
- CRISPR and Genetic Engineering
- Ginseng Biological Effects and Applications
- Bone health and treatments
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- Proteoglycans and glycosaminoglycans research
- Connective tissue disorders research
- Inflammatory mediators and NSAID effects
- Tendon Structure and Treatment
Stanford University
2024-2025
VA Palo Alto Health Care System
2024-2025
Southern University of Science and Technology
2020-2024
Hong Kong Baptist University
2016-2022
Shenzhen Institute for Drug Control
2017
Unimed Medical Institute
2017
Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to tumor site. By connecting tumor-targeting aptamer (NucA) active hydroxyl group at 2' position of via cathepsin B sensitive dipeptide bond, NucA-PTX remains...
Intervertebral disc (IVD) degeneration (IVDD) is the main cause of low back pain with major social and economic burdens; however, its underlying molecular mechanisms remain poorly defined. Here we show that focal adhesion protein Kindlin-2 highly expressed in nucleus pulposus (NP), but not anulus fibrosus cartilaginous endplates, IVD tissues. Expression drastically decreased NP cells aged mice severe IVDD patients. Inducible deletion adult causes spontaneous striking IVDD-like phenotypes...
Osteoarthritis (OA) is a devastating whole-joint disease affecting large population worldwide with no cure; its mechanism remains poorly defined. Abnormal mechanical stress the main pathological factor of OA. To investigate effects Piezo1 activation on osteoarthritis development and progression to explore Piezo1-targeting OA treatment. The expression levels were determined in human cartilage experimental mice. Mice genetic deletion chondrocytes or intra-articular injection activator Yoda1...
Abstract Rheumatoid arthritis (RA) is an autoimmune disease. Early studies hold opinion that gut microbiota environmentally acquired and associated with RA susceptibility. However, accumulating evidence demonstrates genetics also shape the microbiota. It known some strains of inbred laboratory mice are highly susceptible to collagen-induced (CIA), while others resistant CIA. Here, we show transplantation fecal CIA-resistant C57BL/6J CIA-susceptible DBA/1J confer CIA resistance in mice....
In vertebrates, the type 1 parathyroid hormone receptor (PTH1R) is a critical regulator of skeletal development and homeostasis; however, how it modulated incompletely understood. Here we report that deleting Kindlin-2 in osteoblastic cells using mouse 10-kb Dmp1-Cre largely neutralizes intermittent PTH-stimulated increasing bone volume fraction mineral density by impairing both osteoblast osteoclast formation murine adult bone. Single-cell profiling reveals loss increases proportion...
Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in pathology and potential treatment To investigate effects disc-specific Piezo1 deletion, we generated Aggrecan CreERT2 ; fl/fl mice examined both lumbar spine instability (LSI)- aging-induced Additionally, effect pharmacological inhibition was evaluated using GsMTx4, potent antagonist, an ex...
Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide originally developed to suppress inflammation via its metabolite A77 1726 attenuate However, distinctive responsiveness observed among RA individuals. Here we show that exerts immunosuppression but limited efficacy in individuals distinguished higher serum C-reactive protein (CRP Higher , CRP H ), whereas the others with satisfactory lower Lower L ). inhibition...
Abstract The progressive destruction of condylar cartilage is a hallmark the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism incompletely understood. Here, we show that Kindlin-2, key focal adhesion protein, strongly detected in cells mandibular mice. We find genetic ablation Kindlin-2 aggrecan-expressing chondrocytes induces multiple spontaneous osteoarthritic lesions, including loss and deformation, surface fissures, ectopic bone formation TMJ. significantly...
Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging-associated diseases. Smad-dependent canonical BMP signaling pathway is indispensable for osteoblastic bone formation, which could be disrupted by and subsequent proteasomal degradation Smad1/5, key molecules transduction. However, whether Smad1/5 responsible age-related formation reduction still underexplored. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) previously...
Genetically modified mice are the most useful tools for investigating gene functions in articular cartilage biology and pathogenesis of osteoarthritis. The AggrecanCreERT2 one reported mouse lines used this purpose. Prg4 (proteoglycan 4) encodes lubricin protein is expressed selectively chondrocytes located at superficial layer cartilage. While Prg4GFPCreERT2 knock-in inducible-Cre transgenic were generated a while ago, so far, few studies have line to perform functional biology.We recently...
In vertebrate,the nucleus pulposus (NP), which is an essential component of the intervertebral disc, constantly impacted by fluid shear stress (FSS); however, molecular mechanism(s) through FSS modulates NP homeostasis poorly understood. Here we show that regulates extracellular matrix (ECM) in cells. A moderate dose (i.e., 12 dyne/cm2) increases sulfated glycosaminoglycan (sGAG) content and protein levels Col2a1 Aggrecan decreases those metalloproteinase 13 (MMP13) a disintegrin with...
Our recent studies demonstrate that the focal adhesion protein Kindlin-2 exerts crucial functions in mesenchymal stem cells, mature osteoblasts and osteocytes control of early skeletal development bone homeostasis mice. However, whether plays a role osteoprogenitors remains unclear. Mice lacking expression osterix (Osx)-expressing cells (i.e., osteoprogenitors) were generated. Micro-computerized tomography (μCT) analyses, histology, histomorphometry immunohistochemistry performed to...
Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist approximately 60% the transcriptional output cells. Thousands ncRNAs have been identified in recent decades, their essential roles regulation gene expression diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, metabolism,...
Abstract The underlying mechanism of the reduced bone formation during development glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that highly expressed CKIP-1 together with lowly total and phosphorylated Smad1/5 in samples was accompanied by either serum markers GIO patients or decreased mice. In vitro studies showed could promote Smad1 ubiquitination to suppress Smad-dependent BMP signaling inhibit osteogenic differentiation mineral deposition MC3T3-E1 cells...
Osteoarthritis (OA) is the most common degenerative joint disease affecting older populations globally. Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c), a lipid kinase catalyzing synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), involved in various cellular processes, such as focal adhesion (FA) formation, cell migration, and signal transduction. However, whether Pip5k1c plays role pathogenesis OA remains unclear. Here we show that inducible deletion...