Rachelle Johnson
Last active: 3/26/2019

gp130 in late osteoblasts and osteocytes is required for PTH-induced osteoblast differentiation.

Standal T, Johnson RW, McGregor NE, Poulton IJ, Ho PW, Martin TJ, Sims NA
J Endocrinol. 2014 223 (2): 181-90

PMID: 25228504 · DOI:10.1530/JOE-14-0424

Parathyroid hormone (PTH) treatment stimulates osteoblast differentiation and bone formation, and is the only currently approved anabolic therapy for osteoporosis. In cells of the osteoblast lineage, PTH also stimulates the expression of members of the interleukin 6 (IL-6) cytokine superfamily. Although the similarity of gene targets regulated by these cytokines and PTH suggest cooperative action, the dependence of PTH anabolic action on IL-6 cytokine signaling is unknown. To determine whether cytokine signaling in the osteocyte through glycoprotein 130 (gp130), the common IL-6 superfamily receptor subunit, is required for PTH anabolic action, male mice with conditional gp130 deletion in osteocytes (Dmp1Cre.gp130(f/f)) and littermate controls (Dmp1Cre.gp130(w/w)) were treated with hPTH(1-34) (30 μg/kg 5× per week for 5 weeks). PTH dramatically increased bone formation in Dmp1Cre.gp130(w/w) mice, as indicated by elevated osteoblast number, osteoid surface, mineralizing surface, and increased serum N-terminal propeptide of type 1 collagen (P1NP). However, in mice with Dmp1Cre-directed deletion of gp130, PTH treatment changed none of these parameters. Impaired PTH anabolic action was associated with a 50% reduction in Pth1r mRNA levels in Dmp1Cre.gp130(f/f) femora compared with Dmp1Cre.gp130(w/w). Furthermore, lentiviral-Cre infection of gp130(f/f) primary osteoblasts also lowered Pth1r mRNA levels to 16% of that observed in infected C57/BL6 cells. In conclusion, osteocytic gp130 is required to maintain PTH1R expression in the osteoblast lineage, and for the stimulation of osteoblast differentiation that occurs in response to PTH.

© 2014 Society for Endocrinology.

MeSH Terms (14)

Animals Animals, Newborn Cell Differentiation Cells, Cultured Cytokine Receptor gp130 Male Mice Mice, Inbred C57BL Mice, Knockout Osteoblasts Osteocytes Osteogenesis Parathyroid Hormone Receptor, Parathyroid Hormone, Type 1

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