Role of inflammation in atherosclerotic calcification, metaplasia and osteoporosis

摘要

It is not unusual for atherosclerotic lesions to contain ectopic tissue, including bone, cartilage, fat and marrow.It is also common for patients with atherosclerosis to have osteoporosis. Thus, in many elderly patients, bone is forming in their artery walls at the same time as bone is being permanently lost from their skeleton. The stimuli and mechanisms underlying these reciprocal processes are not understood One clue is that adult tissues, such as bone marrow stroma and adipose tissue, contain mesenchymal stem cells (MSC) with the potential to form bone, cartilage, muscle and fat as well as the potential for self-renewal.We previously found that a subpopulation of cells harvested from normal aortic tunica media have the capacity for differentiation along the osteogenic lineage, which is enhanced by inflammatory factors including cytokines, oxidized lipids, and lipoproteins. But true osteoblasts derived from bone were inhibited by treatment with these same factors, and adipogenesis was favored over osteogenic differentiation in the marrow precursor cells of hyperlipidemic animals. The same inflammatory factors enhanced bone resorptive osteoclastic activity.These findings suggest mechanisms for simultaneous atherosclerotic calcification and osteoporosis.We have now investigated whether the subpopulation of cells with osteogenic potential has the potential to differentiation along other lineages. The findings have important therapeutic implications for use of stem cells in regenerative therapy and tissue bioengineering.