zaprinast and Osteoporosis--Postmenopausal

It is well known that osteoporosis is a significant chronic disease with the increase of the aging population. Here, we report that expression of G protein-coupled receptor 35 (GPR35) in bone marrow mesenchymal stem cells (BMSCs) is suppressed in diagnosed osteoporosis patients and osteoporotic mice. The expression of GPR35 on BMSCs is enhanced during osteogenic differentiation. GPR35 knockout suppresses the proliferation and osteogenesis of BMSCs and deteriorates bone mass in both sham-treated and ovariectomized mice. Moreover, GPR35 deficiency reduces β-catenin activity in BMSCs. In contrast, the overexpression of GPR35 contributes to these processes in BMSCs. Finally, using zaprinast, a synthetic GPR35 agonist, we show that zaprinast rescues OVX-induced bone loss and promotes bone generation in mice. Thus, GPR35 may as a new target and its agonist zaprinast may serve as a novel treatment for osteoporosis.

Topics: Animals; beta Catenin; Bone and Bones; Bone Density; Bone Marrow Cells; Cell Proliferation; Female; Glycogen Synthase Kinase 3 beta; Humans; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Organ Size; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; Purinones; Receptors, G-Protein-Coupled; Wnt Signaling Pathway