Dose-dependent tandem responses of osteoblasts during osteogenesis

Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedependent relationship between irisin and bone formation remain unclear.In this study,we explored the dosedependent effects of irisin on osteoblast proliferation and differentiation.Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin,which was further enhanced over time.Notably,this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ng/ml and 100 ng/ml.Furthermore,we determined that 1,10,and 100 ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors(Runx2,Osx,and Atf4),as well as osteogenic markers(Alp,Col1a1 and Spp1),albeit without significant difference among these 3 concentrations.Interestingly,nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation.Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.

Interaction of arterial proteoglycans with low density lipoproteins(LDLs):From theory to promising therapeutic approaches

Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)are usually composed of one core protein backbone with one or more glycosaminoglycan chains(GAGs)covalently linked,mainly include perlecan,biglycan,versican,and decorin.The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100,the moiety of LDL,electrostatic interacting with the negatively charged GAGs(sulfate or carbohydrate groups)of proteoglycans or though some bridge molecules like sphingomyelinase(SMase)or lipoprotein lipase(LpL).In the later section,we collate the promising therapeutic approaches that have been proposed up to now,targeting LDL-PGs interaction.It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan,biglycan,decorin,and versican that all located in the extracellular matrix(ECM),future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs,seeking promising therapeutic targets more specifically.