Aberrant gene expression in cultured mammalian bone cells demonstrates an osteoblast defect in osteopetrosis

UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Animals; Bone and Bones; Cells, Cultured; Gene Expression Regulation; Osteoblasts; Osteopetrosis; Rats; Rats, Mutant Strains


Cell Biology


Osteopetrosis is a skeletal condition in which a generalized radioopacity of bone is caused by reduced resorption of bone by osteoclasts. However, it has recently been shown that during skeletal development in several osteopetrotic rat mutations specific aberrations occur in gene expression reflecting the activity of the bone forming cells, osteoblasts, and the development of tissue organization. To evaluate their pathogenetic significance, progressive osteoblast differentiation was studied in vitro. Primary cultures of normal osteoblasts undergo a sequential expression of cell growth and tissue-related genes associated with development of skeletal tissue. We report that osteoblast cultures can be established from one of these mutants, toothless; that these cells in vitro exhibit similar aberrations in gene expression during cell proliferation and extracellular matrix formation and mineralization observed in vivo; and that an accelerated maturation sequence by mutant osteoblasts mimics the characteristic skeletal sclerosis of this disease. These data are the first direct evidence for an intrinsic osteoblast defect in osteopetrosis and establish an in vitro model for the study of heritable skeletal disorders.

DOI of Published Version



J Cell Biochem. 1994 Jul;55(3):366-72. Link to article on publisher's site

Journal/Book/Conference Title

Journal of cellular biochemistry

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PubMed ID