Exposure to second-hand cigarette smoke exacerbates the progression of osteoarthritis in a surgical induced murine model.

Osteoarthritis (OA), formerly understood to be a result of passive wear, is now known to be associated with chronic inflammation. Cigarette smoking promotes systemic inflammation and has been implicated in increased joint OA incidence in some studies, though the recent observational data on the association are contradictory. We hypothesize that second-hand smoke (SHS) treatment will increase the incidence of OA in a mouse model that has been subjected to a surgical destabilization of the medial meniscus (DMM).

Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by inflammatory degradation of articular cartilage and subchondral bone. Wogonin, a compound extracted from the plant (colloquially known as skullcap), has previously been shown to have direct anti-inflammatory and antioxidative properties. We examined the pain-reducing, anti-inflammatory, and chondroprotective effects of wogonin when applied as a topical cream.

Osteoarthritis-Like Changes in Bardet-Biedl Syndrome Mutant Ciliopathy Mice (): Evidence for a Role of Primary Cilia in Cartilage Homeostasis and Regulation of Inflammation.

Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple "wear and tear" disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet-Biedl mice.

Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure.

Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events.

A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology.

Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases.

Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse.

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA.

Inflammatory markers associated with osteoarthritis after destabilization surgery in young mice with and without Receptor for Advanced Glycation End-products (RAGE).

HtrA1, Ddr-2, and Mmp-13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA-1 is unknown. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TGF-β and the Receptor for Advanced Glycation End-products (RAGE). To examine the correlation of inflammation with the expression of biomarkers in OA, we performed right knee destabilization surgery on 4-week-old-wild type and RAGE knock-out (KO) mice.

Expression of vascular endothelial growth factor and endothelial nitric oxide synthase is increased in the placenta of sheep at high altitude in the Andes.

Fetal weight and the placenta of sheep at high altitude (HA) are affected by hypoxia. Placental changes (an increase in placental size and vascularization) are greater in ewes from populations that have lived for several generations at HA than in those exposed during just 1 gestation. This study investigated placental expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), 2 molecules involved in placental angiogenesis that could be upregulated by hypoxia.

Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice.

Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30-50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight.

Foundation Review: Transgenic animals and their impact on the drug discovery industry.

The ability to direct genetic changes at the molecular level has resulted in a revolution in biology. Nowhere has this been more apparent than in the production of transgenic animals. Transgenic technology lies at the junction of several enabling techniques in such diverse fields as embryology, cell biology and molecular genetics.