Regulation of osteoblastic gene expression by lead

Research output: Contribution to journalArticle

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Abstract

Although it is well recognized that lead accumulates in bone, skeletal tissue is considered primarily a sequestering compartment and not a site of toxic action for lead. However, exposure to lead is associated with impaired skeletal growth in children and reductions in indices of bone formation in laboratory animals. Osteoblastic ROS 17/2.8 cells were used in an effort to better understand the consequences of lead exposure on skeletal homeostasis. Studies on confluent cultures of ROS 17/2.8 cells revealed that lead (2-200 μM) had no effect on cell number or DNA and protein synthesis. However, alkaline phosphatase activity was reduced by lead in a dose- and time-dependent manner. Reductions in steady state alkaline phosphatase mRNA levels paralleled the lead-induced inhibition of enzyme activity. Moreover, lead exposure resulted in similar dose-dependent reductions in steady state type 1 procollagen and bone Gla protein mRNA levels. The effort of lead on osteoblastic gene expression in ROS 17/2.8 cultures, however, was selective in nature, as similar lead exposures resulted in no alterations in β-actin or glyceraldehyde-3-phosphate dehydrogenase mRNA levels. These data demonstrate that lead, in the absence of overt toxicity, specifically restricts the expression of certain aspects of the differentiated osteoblast phenotype. Such alterations in osteoblast function may contribute to the skeletal abnormalities observed in settings of lead intoxication.

Original languageEnglish (US)
Pages (from-to)2531-2537
Number of pages7
JournalEndocrinology
Volume132
Issue number6
StatePublished - Jun 1993

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Gene Expression Regulation
Osteoblasts
Messenger RNA
Alkaline Phosphatase
Lead
Toxic Actions
Glyceraldehyde-3-Phosphate Dehydrogenases
Osteocalcin
Laboratory Animals
Collagen Type I
Osteogenesis
Actins
Homeostasis
Cell Count
Phenotype
Gene Expression
Bone and Bones

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulation of osteoblastic gene expression by lead. / Klein, Robert; Wiren, Kristine.

In: Endocrinology, Vol. 132, No. 6, 06.1993, p. 2531-2537.

Research output: Contribution to journalArticle

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