Amphiregulin lacks an essential role for the bone anabolic action of parathyroid hormone.

Abstract:

:Although parathyroid hormone (PTH) has long been known to act as a bone anabolic agent when administered intermittently, the exact underlying mechanisms remain largely unknown. Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, has been identified to be a PTH target gene in vitro and in vivo. Here, we used female global AREG knockout (AREG-KO) mice to explore the role of AREG in mediating the bone anabolic effects of PTH. AREG-KO mice were characterized by unchanged distal femoral cancellous bone mass and only subtle decreases in bone mineral density (BMD) and cortical thickness at the femoral midshaft at 3 and 8 months of age, relative to wildtype controls. AREG deficiency was associated with complex changes in the mRNA expression of other EGFR ligands in femoral cancellous bone osteoblasts in situ in 3-week-old mice. To examine the bone anabolic effects of PTH in the absence and presence of AREG, we injected 3-month-old AREG-KO females and wildtype control littermates with 80 μg/kg PTH or vehicle 5 times per week over 4 weeks. Intermittent PTH treatment of AREG-KO mice led to increases in femoral trabecular and cortical BMD, cortical thickness, endocortical and periosteal bone formation, cancellous bone formation rate, and serum osteocalcin, comparable to those observed in wildtype control mice. In conclusion, our data indicate that the bone anabolic effects of PTH do not require AREG, at least in 3-month-old female mice.

journal_name

Mol Cell Endocrinol

authors

Jay FF,Vaidya M,Porada SM,Andrukhova O,Schneider MR,Erben RG

doi

10.1016/j.mce.2015.09.031

subject

Has Abstract

pub_date

2015-12-05 00:00:00

pages

158-65

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(15)30097-6

journal_volume

417

pub_type

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