Hormonal and systemic regulation of sclerostin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The Wnt/β-catenin signaling pathway plays an essential role in osteoblast biology. Sclerostin is a soluble antagonist of Wnt/β-catenin signaling secreted primarily by osteocytes. Current evidence indicates that sclerostin likely functions as a local/paracrine regulator of bone metabolism rather than as an endocrine hormone. Nonetheless, circulating sclerostin levels in humans often reflect changes in the bone microenvironment, although there may be exceptions to this observation. Using existing assays, circulating sclerostin levels have been shown to be altered in response to both hormonal stimuli and across a variety of normal physiological and pathophysiological conditions. In both rodents and humans, parathyroid hormone provided either intermittently or continuously suppresses sclerostin levels. Likewise, most evidence from both human and animal studies supports a suppressive effect of estrogen on sclerostin levels. Efforts to examine non-hormonal/systemic regulation of sclerostin have in general shown less consistent findings or have provided associations rather than direct interventional information, with the exception of mechanosensory studies which have consistently demonstrated increased sclerostin levels with skeletal unloading, and conversely decreases in sclerostin with enhanced skeletal loading. Herein, we will review the existent literature on both hormonal and non-hormonal/systemic factors which have been studied for their impact on sclerostin regulation.

Original languageEnglish (US)
JournalBone
DOIs
StateAccepted/In press - Jul 28 2016

Fingerprint

Catenins
Hindlimb Suspension
Bone and Bones
Osteocytes
Wnt Signaling Pathway
Osteoblasts
Rodentia
Estrogens
Hormones
human PTH protein

Keywords

  • Bone
  • Diabetes
  • Estrogen
  • Hormone
  • Loading
  • Osteocyte
  • Parathyroid
  • Sclerostin
  • Unloading

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

Cite this

Hormonal and systemic regulation of sclerostin. / Drake, Matthew M; Khosla, Sundeep.

In: Bone, 28.07.2016.

Research output: Contribution to journalArticle

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