Adiponectin Stimulates Osteoblast Differentiation Through Induction of COX2 in Mesenchymal Progenitor Cells

Abstract

In bone marrow, osteoblasts and adipocytes are differentiated from mesenchymal progenitor cells and their differentiation is reciprocally regulated by largely unknown mechanisms. In this study, we investigated downstream signaling cascades of adiponectin, a member of the adipocytokine family, in the regulation of osteoblast differentiation. Adiponectin augmented expression of several osteogenic marker genes and increased osteoblast differentiation in mesenchymal progenitor cells. The expression of cyclooxygenase-2 (COX2) was potently increased by adiponectin, whereas inhibition of COX2 activity abolished the effect of adiponectin on osteogenesis. In addition, adiponectin rapidly stimulated p38 mitogen-activated protein kinase via the adiponectin receptor, AdipoR1, which resulted in c-Jun activation for COX2 expression. Adiponectin also stimulated BMP2 expression in a COX2-dependent manner. Moreover, Runx2, a key osteogenic transcription factor, contributed to the acceleration of osteogenesis in the presence of adiponectin. Collectively, the finding that adiponectin could promote osteogenesis through an intracellular signaling cascade in mesenchymal progenitor cells suggests that adiponectin would be a potential therapeutic target for bone-related diseases.

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

“…147 Paradoxically, adiponectin which is secreted nearly exclusively by adipocytes has been found to prevent adipogenic differentiation in bone marrow cultures and increase trabecular bone mass by promoting osteoblastogenesis and repressing osteoclast formation. [148][149][150][151] Unlike adiponectin, the expression of leptin increases concurrently with adiposity and appears to be unaffected by diabetes. [152][153][154] Leptin appears to have contradictory effects on bone, activating the sympathetic nervous system to accelerate bone loss, as well as stimulating the osteogenic differentiation of marrow MPCs, with the net outcome dependent on its concentration.…”

Clinical immunology Comparison of phenotype, chondrogenic and osteogenic potential of rheumatoid mesenchymal stem cells derived from articular and subcutaneous adipose tissue - the role of adipocytokines

“…Among published data there is no reports concerning adiponectin isoforms effect on these cells differentiation. However, total adiponectin was shown to enhance chondrocyte differentiation and mesenchymal stem cells osteoblastic differentiation [19,20].…”

Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty

“…Exercise increases adiponectin levels, and this may maintain a normal BMD in BDs. It has been reported that adiponectin promotes osteogenesis, increasing osteogenic markers and augmenting osteoblast differentiation (42).…”