Regulation of pregnancy-associated plasma protein-A expression in cultured human osteoblasts

Cheryl A. Conover, Bing Kun Chen, Zachary T. Resch

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase secreted by cultured human osteoblasts that has been implicated in the regulation of local insulin-like growth factor (IGF) bioavailability during bone growth and remodeling. However, very little is known about the regulation of PAPP-A expression in bone. In this study, we determined the effect of systemic and local osteoregulatory factors on PAPP-A mRNA and protein expression in normal human osteoblasts (hOB cells). Treatment of hOB cells with particular peptide growth factors (basic fibroblast growth factor, epidermal growth factor), steroid hormones (dexamethasone, 1,25-dihydroxyvitamin D 3), and cytokines [interleukin-6 (IL-6), IL-13, oncostatin M] with known involvement in bone cell physiology had no significant effect on PAPP-A expression. Agents that increase intracellular cyclic AMP (forskolin, prostaglandin E2) increased PAPP-A mRNA and protein expression ∼3-fold. Tumor necrosis factor α (TNFα), IL-1β, and IL-4 also increased PAPP-A expression 3- to 4-fold. Transforming growth factor β (TGFβ) was previously shown to stimulate PAPP-A expression in hOB cells. The effects of TGFβ, TNFα, and IL-1β were additive, whereas the effects of TGFβ and IL-4 were synergistic. In summary, TNFα, IL-1β, and IL-4 were identified as potent stimulators of PAPP-A expression in primary cultures of human osteoblasts. These findings suggest a mechanism whereby cytokines present in bone and bone marrow could augment IGF bioavailability during skeletal growth and remodeling.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalBone
Volume34
Issue number2
DOIs
StatePublished - Feb 2004

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Keywords

  • Cytokines
  • Human osteoblasts
  • Insulin-like growth factor
  • Pregnancy-associated plasma protein-A

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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