Data from: Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis

Obesity has always been considered a significant risk factor in OA
progression, but the underlying mechanism of obesity-related inflammation
in OA synovitis remains unclear. The present study found that synovial
macrophages infiltrated and polarized in the obesity microenvironment and
identified the essential role of M1 macrophages in impaired macrophage
efferocytosis using pathology analysis of obesity-associated OA. The
present study revealed that obese OA patients and Apoe-/- mice showed a
more pronounced synovitis and enhanced macrophage infiltration in synovial
tissue, accompanied by dominant M1 macrophage polarization. Obese OA mice
had more severe cartilage destruction and increased levels of synovial
apoptotic cells than OA mice in the control group. Enhanced M1-polarized
macrophages in obese synovium decreased growth arrest-specific 6 (GAS6)
secretion, resulting in impaired macrophage efferocytosis in synovial
apoptotic cells. Intracellular contents released by accumulated apoptotic
cells further triggered an immune response and lead to a release of
inflammatory factors, such as TNF-α, IL-1β, and IL-6, which induce
chondrocyte homeostasis dysfunction in obese OA patients. Intra-articular
injection of GAS6 restored the phagocytic capacity of macrophages, reduced
the accumulation of local apoptotic cells, and decreased the levels of
TUNEL- and caspase-3-positive cells, preserving cartilage thickness and
preventing the progression of obesity-associated OA. Therefore, targeting
macrophage-associated efferocytosis or intra-articular injection of GAS6
is a potential therapeutic strategy for obesity-associated OA.