Osteoblastic cell secretome: A novel role for progranulin during risedronate treatment

Abstract

It is well established that osteoblasts, the key cells involved in bone formation during development and in adult life, secrete a number of glycoproteins harbouring autocrine and paracrine functions. Thus, investigating the osteoblastic secretome could yield important information for the pathophysiology of bone. In the present study, we characterized for the first time the secretome of human Hobit osteoblastic cells. We discovered that the secretome comprised 89 proteins species including the powerful growth factor progranulin. Recombinant human progranulin (6 nM) induced phosphorylation of mitogen-activated protein kinase in both Hobit and osteocytic cells and induced cell proliferation and survival. Notably, risedronate, a nitrogen-containing bisphosphonate widely used in the treatment of osteoporosis, induced the expression and secretion of progranulin in the Hobit secretome. In addition, our proteomic study of the Hobit secretome revealed that risedronate induced the expression of ERp57, HSP60 and HSC70, three proteins already shown to be associated with the prevention of bone loss in osteoporosis. Collectively, our findings unveil novel targets of risedronate-evoked biological effects on osteoblast-like cells and further our understanding of the mechanisms of action of this corrently used compound.

Progranulin concentration in relation to bone mineral density among obese individuals

“…Documented results showed that recombinant human PGRN can induce phosphorylation of mitogenactivated protein kinase in both HOBIT and osteocytic cells and induce cell proliferation and survival. Moreover, they found that Risedronate, a widely used bisphosphonate drug in the treatment of osteoporosis, can induce the expression and secretion of PGRN in the HOBIT secretome (16). These findings have shown the probable preventive effects of PGRN on osteoporosis by modulating bone loss.…”

“…Similarly to this study, Romanello and cols. demonstrated the proliferative and pro-survival effects of PRGN on osteocyte-like cells (16). Likewise, a recent study by Oh and cols.…”

“…Moreover, the authors reported that Risedronate, a bisphosphonate drug which has been widely used in the treatment of osteoporosis, induces the expression as well as the secretion of PRGN in the HOBIT secretome. These findings suggested the possible role of PGRN in osteoblast/osteocyte biology (16).…”

Bone Conditioned Medium: Preparation and Bioassay

“…For our purposes, BCM can be prepared from fresh pig mandibles 10,11 . Proteomic analyses of BCM revealed the complex composition, including growth factors and constituents of the extracellular matrix 10 , also extending existing knowledge on the proteasome of whole bone 18,19 . Thus, BCM should reflect the released activity of various modifications of bone grafts in vitro.…”

Progranulin and a Five Transmembrane Domain-Containing Receptor-like Gene Are the Key Components in Receptor Activator of Nuclear Factor κB (RANK)-dependent Formation of Multinucleated Osteoclasts

“…Hence, the importance of PGRN in inflammation remains quite controversial and may need to be clarified in other inflammatory diseases involving osteoporosis. More recently, it has been shown that OBs produce a great deal of PGRN, which affects chondrogenesis (17). Therefore, we are interested in the roles of PGRN in bone biology.…”