Synovial macrophages promote TGF-β signaling and protect against influx of S100A8/S100A9-producing cells after intra-articular injections of oxidized low-density lipoproteins.

Objective: Low-density lipoproteins (LDL) in inflamed synovium is oxidized and taken-up by synoviocytes. In this study, we investigate whether direct injection of oxidized LDL (oxLDL) into a normal murine knee joint induces joint pathology and whether synovial macrophages are involved in that process.

Design: Synovium was obtained from end-stage osteoarthritis (OA) patients in order to analyze LDL-uptake.

High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis.

Objective: A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels independent of weight.

Method: Wild type (WT), Apoe(-)(/-), S100a9(-/-) and Apoe(-)(/-)S100a9(-/-) mice (C57BL/6 background) received a standard or cholesterol-rich diet.

High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis?

There is increasing evidence that low-density lipoprotein (LDL) cholesterol plays a role in the pathology of OA. Specifically, oxidized LDL (oxLDL), which has been shown to play an essential role during development of atherosclerosis, could be involved in processes such as synovial inflammation, cartilage destruction and bone deformations. OxLDL can activate synovial cells such as macrophages, endothelial cells and synovial fibroblasts, resulting in release of growth factors, MMP and pro-inflammatory cytokines.

Alarmins S100A8/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis.

Objective: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in osteophyte formation during experimental OA and whether S100A8/A9 predicts osteophyte progression in early human OA.

Methods: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation.

Cholesterol accumulation caused by low density lipoprotein receptor deficiency or a cholesterol-rich diet results in ectopic bone formation during experimental osteoarthritis.

Introduction: Osteoarthritis (OA) is associated with the metabolic syndrome, however the underlying mechanisms remain unclear. We investigated whether low density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial macrophages and affects synovial activation, cartilage destruction and enthesophyte/osteophyte formation during experimental OA in mice.

Methods: LDL receptor deficient (LDLr-/-) mice and wild type (WT) controls received a cholesterol-rich or control diet for 120 days.