Osteoblasts from the toothless (osteopetrotic) mutation in the rat are unable to direct bone resorption by normal osteoclasts in response to 1,25-dihydroxyvitamin D.

Abstract

Osteopetrosis describes a diversified group of metabolic bone disorders characterized by a generalized, skeletal sclerosis resulting from reduced osteoclast-mediated bone resorption. The toothless (tl) osteopetrotic mutation in the rat is characterized by few osteoclasts and the inability to be cured by transplants of hemopoietic stem cells. This implies that the defect(s) responsible for reduced osteoclast activity in tl rats is within the skeletal microenvironment (cells or matrices). Osteoblasts and their products are known to play a role in regulating bone resorption and abnormalities in the osteoblast population in tl rats have been reported. The purpose of this study was to determine whether osteoblasts isolated from tl mutant rats, when cultured with normal osteoclasts, could increase bone resorption (pit formation) in response to stimulation by 1,25 dihydroxyvitamin D (1,25(OH)2D). The addition of 1,25(OH)2D produced a highly significant response in normal osteoblast cocultures but no response in mutant cultures. A dose response study with 1,25(OH)2D (10(-6) to 10(-9)M) revealed that mutant osteoblasts are unable to increase osteoclast activity. These data indicate that the vitamin D receptor-signal transduction pathway in tl rats needs to be examined.

• Authors: K T Sundquist, M E Jackson, D C Hermey, S C Marks Jr
• Journal: Tissue & cell (Tissue Cell) Vol. 27 Issue 5 Pg. 569-74 (Oct 1995) ISSN: 0040-8166 [Print] Scotland
• PMID: 7491626 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcitriol

Topics

• Animals
• Bone Resorption (physiopathology)
• Calcitriol (pharmacology)
• Cells, Cultured
• Coculture Techniques
• Osteoblasts (pathology, physiology)
• Osteoclasts (pathology, physiology)
• Osteopetrosis (genetics, pathology, physiopathology)
• Rats
• Rats, Mutant Strains