Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination Inhibits Proinflammatory COX-2 Expression and Prostaglandin E2 Production in Tendon-Derived Cells.

Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2) could be attenuated by the combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS). ASU, GLU, and CS have been used in the management of osteoarthritis-associated joint inflammation. Tenocytes in monolayer and microcarrier spinner cultures were incubated with media alone, or with the combination of ASU (8.3 µg/mL), GLU (11 µg/mL), and CS (20 µg/mL). Cultures were next incubated with media alone, or stimulated with interleukin-1ß (IL-1ß; 10 ng/mL) for 1 h to measure COX-2 gene expression, or for 24 h to measure PGE2 production, respectively. Tenocyte phenotype was analyzed by phase-contrast microscopy, immunocytochemistry, and Western blotting. Tendon-derived cells proliferated and produced extracellular matrix component type I collagen in monolayer and microcarrier spinner cultures. IL-1ß-induced COX-2 gene expression and PGE2 production were significantly reduced by the combination of (ASU+GLU+CS). The suppression of IL-1ß-induced inflammatory response suggests that (ASU+GLU+CS) may help attenuate deleterious inflammation in tendons.

Seoul virus suppresses NF-kappaB-mediated inflammatory responses of antigen presenting cells from Norway rats.

Hantavirus infection reduces antiviral defenses, increases regulatory responses, and causes persistent infection in rodent hosts. To address whether hantaviruses alter the maturation and functional activity of antigen presenting cells (APCs), rat bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) were generated and infected with Seoul virus (SEOV) or stimulated with TLR ligands. SEOV infected both DCs and macrophages, but copies of viral RNA, viral antigen, and infectious virus titers were higher in macrophages. The expression of MHCII and CD80, production of IL-6, IL-10, and TNF-alpha, and expression of Ifnbeta were attenuated in SEOV-infected APCs. Stimulation of APCs with poly I:C prior to SEOV infection increased the expression of activation markers and production of inflammatory cytokines and suppressed SEOV replication. Infection of APCs with SEOV suppressed LPS-induced activation and innate immune responses. Hantaviruses reduce the innate immune response potential of APCs derived from a natural host, which may influence persistence of these zoonotic viruses in the environment.

Consil bioactive glass particles enhance osteoblast proliferation and selectively modulate cell signaling pathways in vitro.

Consil Bioglass is a commercially available bioactive glass formulation previously shown in clinical studies to support osteogenesis and the repair of bony defects in dogs and cats. Previous in vitro studies confirm that Consil particles are able to bond directly with bone while promoting osteoblast proliferation and extracellular matrix production. However, the cellular mechanisms mediating their clinical effect remain unclear. This study evaluated whether enhancement of osteoblast proliferation by Consil particles is associated with signal transduction. Consil particles maintained the osteoblast phenotype and enhanced proliferation of canine osteoblasts for up to 21 days in culture. Stimulation of proliferation and maintenance of phenotype expression were accompanied by the modulation of selective cell signaling pathways including integrins, the mitogen-activated protein kinases (MAPKs), and the immediate-early gene c-Jun. These genes have been documented to mediate osteoblast growth and differentiation. The signal transduction occurs in a time-dependent manner in which Consil particles induce a decrease in the pattern of MAPK and c-Jun gene transcription from 4 to 24 h and a subsequent return to control levels by 7 days in culture. Our observations suggest that Consil Bioglass particles may provide cues that enhance cell division necessary for facilitating bone regeneration and the repair of bony defects.

Consil bioactive glass particles enhance osteoblast proliferation and maintain extracellular matrix production in vitro.

Bioactive glasses are used clinically as bone implant materials as they are able to bond directly with bone. Studies in dogs have demonstrated the utility of Consil Bioglass synthetic bone graft particulate, a commercially available bioactive glass formulation, as a bone substitute for repair of bony defects. We evaluated the effect of Consil particles (500 microg/mL) on osteoblast proliferation and extracellular matrix (ECM) production at the cellular level in vitro. An osteoblast surrogate MG-63 cell line was incubated with Consil particles or medium alone for different time periods to determine the effect of Consil particles on proliferation and expression of ECM components. Osteoblasts remained viable and proliferated upon exposure to the particles, as shown by increased total DNA content. Cells incubated with Consil particles maintained expression levels of phenotype markers (type I collagen, osteocalcin, proteoglycans, and alkaline phosphatase) similar to control cells. Levels of secreted type I collagen and osteocalcin were time-dependent and similar to controls. This study verified the ability of Consil particles to enhance proliferation of osteoblast-like cells. The particles also maintained ECM production up to 21 days in culture. Our study supports the reported clinical utility of Consil particles for the repair of bony defects.