A5003148480- Osteoarthritis Treatment and Mechanisms
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Peroxisome Proliferator-Activated Receptors
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Lower Extremity Biomechanics and Pathologies
- Connective tissue disorders research
- Autophagy in Disease and Therapy
- Mast cells and histamine
- Muscle metabolism and nutrition
- Circular RNAs in diseases
- Autoimmune and Inflammatory Disorders Research
- Angiogenesis and VEGF in Cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Calpain Protease Function and Regulation
- Knee injuries and reconstruction techniques
- RNA regulation and disease
- Histiocytic Disorders and Treatments
The University of Texas Health Science Center at Houston
2017-2024
American Journal Experts (United States)
2018
Cartilage oligomeric matrix protein (COMP), a secreted glycoprotein synthesized by chondrocytes, regulates proliferation and type II collagen assembly. Mutations in the COMP gene cause pseudoachondroplasia multiple epiphyseal dysplasia. Previously, we have shown that expression of D469del-COMP transgenic mice causes intracellular retention D469del-COMP, thereby recapitulating chondrocyte pathology. This inducible mouse is only vivo model to replicate critical cellular clinical features...
Pseudoachondroplasia (PSACH), a severe short-limb dwarfing condition, results from mutations that cause misfolding of the cartilage oligomeric matrix protein (COMP). Accumulated COMP in growth plate chondrocytes activates endoplasmic reticulum stress, leading to inflammation and chondrocyte death. Using MT-COMP mouse model PSACH recapitulates molecular clinical phenotype, we previously reported oxidative stress play important unappreciated roles pathology. In this study, assessed ability...
Mutations in the gene encoding cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia (PSACH), a severe dwarfing condition. Pain, significant complication, has generally been attributed to joint abnormalities and erosion early onset osteoarthritis. Previously, we found that inflammatory-related transcripts were elevated growth plate articular cartilages, indicating inflammation plays an important role chondrocyte disease pathology may contribute overall pain sequelae. Here,...
Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using MT-COMP mouse model of PSACH that has common D469del mutation. Mutant-COMP does not fold properly, it retained rough endoplasmic reticulum (rER) chondrocytes rather than being exported to extracellular (ECM), driving ER stress...
Misfolding mutations in cartilage oligomeric matrix protein (COMP) cause it to be retained within the endoplasmic reticulum (ER) of chondrocytes, stimulating a multitude damaging cellular responses including ER stress, inflammation, and oxidative which ultimately culminates death growth plate chondrocytes pseudoachondroplasia (PSACH). Previously, we demonstrated that an antioxidant, resveratrol, substantially reduces intracellular accumulation mutant-COMP, dampens lowers level chondrocyte...
Mutations in cartilage oligomeric matrix protein cause pseudoachondroplasia, a severe disproportionate short stature disorder. Mutant produces massive intracellular retention of protein, stimulating ER and oxidative stresses inflammation, culminating post-natal loss growth plate chondrocytes, which compromises linear bone growth. Treatments for pseudoachondroplasia are limited because is relatively avascular considered inaccessible. Here we report successful delivery treatment using...
Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia associated with premature joint degeneration, is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur articular chondrocytes of MT-COMP mice, murine model PSACH. The accumulation mutant-COMP the ER occurred early and stimulated inflammation (TNFα) at 4 weeks, chondrocyte death increased 8 weeks while through CHOP was elevated 12 weeks....
Mutations in cartilage oligomeric matrix protein (COMP) causes misfolding and accumulation chondrocytes that compromises skeletal growth joint health pseudoachondroplasia (PSACH), a severe dwarfing condition. Using the MT-COMP mice, murine model of PSACH, we showed pathological autophagy blockage was key to intracellular mutant-COMP. Autophagy is blocked by elevated mTORC1 signaling, preventing ER clearance ensuring chondrocyte death. We demonstrated resveratrol reduces plate pathology...
Mutations in cartilage oligomeric matrix protein (COMP), a large extracellular glycoprotein expressed musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death loss growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor abnormalities, normal longevity. This suggests reducing mutant wild-type expression...
Abstract Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia, associated with premature joint degeneration is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur articular chondrocytes of MT-COMP mice, murine model PSACH. The accumulation mutant-COMP the ER occurred early and stimulated inflammation (TNFα) at 4 wks. Articular chondrocyte death increased 8 wks through CHOP was elevated 12...
Abstract Misfolding mutations in cartilage oligomeric matrix protein (COMP) cause it to be retained within ER of chondrocytes, stimulating a multitude damaging cellular responses including stress, inflammation and oxidative stress which ultimately culminates the death growth plate chondrocytes pseudoachondroplasia (PSACH). Previously, we demonstrated that an antioxidant, resveratrol, substantially reduces intracellular accumulation mutant COMP, dampens lowers level chondrocyte death. In...
Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These disrupt normal folding, leading to the accumulation of misfolded COMP chondrocytes. The MT-COMP mouse is murine model PSACH that expresses D469del human response doxycycline replicates chondrocyte clinical pathology. basis for mutant-COMP pathology involves endoplasmic reticulum (ER)...