ASK-8007

Obesity is no longer viewed as single entity but rather as a heterogene ous disease with different phenotypes: classical, metabolically healthy, normal weight and osteosarcopenic obesity [2].Those phenotypes overwhe lm traditional characterization by BMI, but they are rather an e xpression of the new emerging paradigm of CardioMetabolic risk: a cluster of visceral fat deposition (also referred to as adiposopathy) , ectopic fat depots, insulin resistance and cytokine/ adi- pokines dysregulation [3].In line with this new view, proving the central role of inflammation would give an integrated perspective on globa l CardioMetabolic risk finally linked to the established concept of vulnerable patient.Out of the bone, macrophages represent the major source of OPN and one of the main targets.The expression of OPN is up- regulated during injury/healing processes when it is deeply involved in inflammation, fi brosis, mineralization, and tissue regeneration. OPN gene expression is tightly regulat ed by a wide range of hormone s, growth factors, cytokines, and drugs.Furt hermore, epigenetic control of OPN expression also exists. H3K9a, H3K27ac, or H3K4 have been reported to upre gulate OPNc expression in at herosclerosis and diabetes. Conversely, less is known about the epigene tic control of the OPN precursor Spp1.However, only one human antibody inhibit- ing both the RGD domain as well as the α9β1 integrin-d ependent cell binding to OPN (ASK8007) has been so far tested in a proof-of-concept study involving patients with rh eumatoid arthritis without clin. improvement.A consensus on these issues might finally clarify potential therap eutic implications of OPN m odulation at several levels ranging from lifestyle modifi- cations, pharmacotherapy, and ev en surgical interventions.