Evidence for constitutive bone morphogenetic protein-2 secretion by M1 macrophages: constitutive auto/paracrine osteogenic signaling by BMP-2 in M1 macrophages

• Autores: Dube, Prabhatchandra R.; Birnbaumer, Lutz; Vazquez, Guillermo
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Biochemical and Biophysical Research Communications. 2017;491(1):154-158
• Materia: CALCIFICACION; OSTEOGENESIS; ENFERMEDADES VASCULARES
• Institución: Pontificia Universidad Católica Argentina

Fil: Dube, Prabhatchandra R. University of Toledo. College of Medicine and Life Sciences. Center for Hypertension and Personalized Medicine. Department of Physiology and Pharmacology; Estados Unidos
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences. Center for Hypertension and Personalized Medicine. Department of Physiology and Pharmacology; Estados Unidos
Abstract: Mechanisms mediating vascular calcification recapitulate osteogenic processes encompassing bone formation and imply participation of bone related proteins such as bone morphogenetic protein-2 (BMP-2). Macrophages are amongst the cells that contribute to vascular ossification by releasing cytokines that induce an osteogenic program in vascular smooth muscle cells, and also by becoming themselves osteoclast-like cells. In inflammatory vascular disease, the macrophage population in the vascular wall is diverse, with the M1 or inflammatory, and the M2 or anti-inflammatory macrophage types being dominant. Yet, the osteogenic potential of M1 and M2 macrophages remains unknown. Prompted by recent studies from our laboratory showing that in macrophages the Transient Receptor Potential Canonical 3 (TRPC3) channel contributes to endoplasmic reticulum (ER) stress-induced apoptosis in M1, but not in M2 macrophages, and given the strong relationship between ER stress and vascular calcification, we wished to examine whether TRPC3 would play a role in the osteogenic signaling of polarized macrophages. The findings reported here indicate that a constitutive BMP-2-dependent signaling operates in M1 macrophages, which is not affected by deletion of Trpc3 and is not subject to regulation by ER stress. Our studies suggest operation of an auto/paracrine mechanism by which BMP-2 secreted by M1 macrophages maintains constitutive activation of a BMP-2 receptor/SMAD1/5 signaling axis.