Experimental studies of osteopetrosis in laboratory animals.

Abstract

Osteopetrosis is a metabolic bone disease characterized by a systemic increase in skeletal mass. It results from a defect in the production or function of osteoclasts and is inherited in nine genetically distinct osteopetrotic animal mutations and man. Studies of these mutations have revealed that osteopetrosis is a complex, heterogeneous disorder in its expression, etiology, and response to treatment by bone marrow transplantation or by hormone/growth factor therapy. These animal mutations have been valuable tools for probing the pathogenesis and treatment of osteopetrosis, and information obtained from these studies has been used clinically for the treatment of humans with osteopetrosis. In addition, studies of these mutations have contributed significantly to understanding normal bone cell biology, including the origin of the osteoclast and the significance of colony-stimulating factor-1 in osteoclast development. The resistance of some of these mutations to cure by stem cell transplantation and hormone therapy, coupled with similar observations and experiences in the human condition, indicates that these animal mutations will continue to serve important roles in the development of alternative therapies to treat resistant forms of the disease. These studies are bound to improve the understanding of normal bone biology by providing additional insights into the regulation of osteoclasts by osteoblasts and their products or by other elements of the skeletal microenvironment.

• Authors: M F Seifert, S N Popoff, M E Jackson, C A MacKay, M Cielinski, S C Marks Jr
• Journal: Clinical orthopaedics and related research (Clin Orthop Relat Res) Issue 294 Pg. 23-33 (Sep 1993) ISSN: 0009-921X [Print] United States
• PMID: 8358920 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Colony-Stimulating Factors
• Dihydroxycholecalciferols

Topics

• Animals
• Bone Marrow Transplantation
• Colony-Stimulating Factors (therapeutic use)
• Dihydroxycholecalciferols (therapeutic use)
• Humans
• Mice
• Mice, Mutant Strains
• Osteoblasts
• Osteoclasts (metabolism)
• Osteopetrosis (congenital, metabolism, therapy)
• Rats
• Rats, Mutant Strains