The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin

Jingzhu Zhang, Adi Cohen, Bo Shen, Liming Du, Alpaslan Tasdogan, Zhiyu Zhao, Elizabeth J. Shane, Sean J. Morrison

Research output: Contribution to journalArticlepeer-review

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 Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin 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 SOSTiinduced 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.

Original languageEnglish (US)
Article numbere2026176118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number25
DOIs
StatePublished - Jun 22 2021

Keywords

  • Osteogenesis
  • Osteolectin
  • Parathyroid hormone
  • Sclerostin
  • Stem cells

ASJC Scopus subject areas

  • General

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