Alpha-7 Nicotinic Receptor Dampens Murine Osteoblastic Response to Inflammation and Age-Related Osteoarthritis.

Introduction: Osteoarthritis (OA) is a whole-joint disease characterized by a low-grade inflammation that is involved in both cartilage degradation and subchondral bone remodeling. Since subchondral bone has a cholinergic innervation and that acetylcholine (Ach) might have an anti-inflammatory effect through the α7 nicotinic Ach receptor (α7nAchR), we aimed (i) to determine the expression of non-neuronal cholinergic system and nicotinic receptor subunits by murine and human osteoblasts, (ii) to address the role of α7nAchR in osteoblastic response to inflammation, and (iii) to study the role of α7nAchR in a spontaneous aging OA model.

Methods: Primary cultures of WT and α7nAchR knock-out mice (Chrna7) murine osteoblasts and of subchondral bone human OA osteoblasts were performed.

Extracellular heat shock proteins and cancer: New perspectives.

Heat shock proteins (HSPs) are a large family of molecular chaperones aberrantly expressed in cancer. The expression of HSPs in tumor cells has been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis. Given that extracellular vesicles (EVs) can serve as potential source for the discovery of clinically useful biomarkers and therapeutic targets, it is of particular interest to study proteomic profiling of HSPs in EVs derived from various biological fluids of cancer patients.

Blockade of IL-33 signalling attenuates osteoarthritis.

Objectives: Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain.

SIRT1 directly activates autophagy in human chondrocytes.

Osteoarthritis (OA) is the most common form of arthritis worldwide with no effective treatment. Ageing is the primary risk factor for OA. We sought to investigate if there is a distinct and functional convergence of ageing-related mechanisms SIRT1 and autophagy in chondrocytes.

Ageing and Osteoarthritis.

The increase in global lifespan has in turn increased the prevalence of osteoarthritis which is now the most common type of arthritis. Cartilage tissue located on articular joints erodes during osteoarthritis which causes pain and may lead to a crippling loss of function in patients. The pathophysiology of osteoarthritis has been understudied and currently no disease modifying treatments exist.

Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300.

Ageing is the primary risk factor for osteoarthritis (OA). A decline in the ageing-associated process of autophagy is suggested as a potential contributor to OA development. Polyamines such as spermidine decrease during ageing, contributing to impaired autophagy and reduced cellular function.

Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior.

Objective: Pain is the most common symptom of osteoarthritis (OA), yet where it originates in the joint and how it is driven are unknown. The aim of this study was to identify pain-sensitizing molecules that are regulated in the joint when mice subjected to surgical joint destabilization develop OA-related pain behavior, the tissues in which these molecules are being regulated, and the factors that control their regulation.

Methods: Ten-week-old mice underwent sham surgery, partial meniscectomy, or surgical destabilization of the medial meniscus (DMM).

Respiratory infections cause the release of extracellular vesicles: implications in exacerbation of asthma/COPD.

Background: Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids.

Aging mechanisms in arthritic disease.

Arthritic disease is one of the most common age-related pathologies worldwide. The erosion of cartilaginous tissues from articular surfaces within the joint and the failure to efficiently repair and regenerate this region with age lead to debilitating joint destruction, severe pain, and a crippling loss of function. In addition to the accumulative damage brought about by years of mechanical forces acting upon this region of tissue, there are also defects in underlying biological mechanisms which predispose the older population to excessive joint erosion.