Increase of Circulating CD11b+Gr1+ cells and Recruitment into the Synovium in Osteoarthritic Mice with Hyperlipidemia

Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis(OA), the link between OA and hyperlipidemia is not fully understood. As the number ofactivated, circulating myeloid cells is increased during hyperlipidemia, we speculate thatmyeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells inSTR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios ofmyeloid cells in bone marrow, the spleen, and peripheral blood were determined by flowcytometry. To examine the influence of the hematopoietic environment, including abnormalstem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantationswere performed. The relationship between hyperlipidemia and abnormal hematopoiesis wasexamined by evaluating biochemical parameters and spleen weight of F₂ animals(STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b⁺Gr1⁺ cellsin spleens and peripheral blood was increased, and CD11b⁺Gr1⁺ cellswere also present in synovial tissue. Splenomegaly was observed and correlated with theratio of CD11b⁺Gr1⁺ cells. When bone marrow from GFP-expressing micewas transplanted into STR/Ort mice, no difference in the percentage ofCD11b⁺Gr1⁺ cells was observed between transplanted and age-matchedSTR/Ort mice. Analysis of biochemical parameters in F₂ mice showed that spleenweight correlated with serum total cholesterol. These results suggest that the increase incirculating and splenic CD11b⁺Gr1⁺ cells in STR/Ort mice originatesfrom hypercholesterolemia. Further investigation of the function ofCD11b⁺Gr1⁺ cells in synovial tissue may reveal the pathology of OAin STR/Ort mice.