The Effect of Parathyroid Hormone on Osteogenesis is Mediated Partly by Osteolectin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2021 Jun 18

PMID 34140410

Citations 17

Authors

Jingzhu Zhang

Adi Cohen

Bo Shen

Liming Du

Alpaslan Tasdogan

Zhiyu Zhao

Elizabeth J Shane

Sean J Morrison

Affiliations

Soon will be listed here.

Abstract

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor (LepR) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

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