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Mechanisms of Osteoclast Dysfunction in Human Osteopetrosis: Abnormal Osteoclastogenesis and Lack of Osteoclast‐Specific Adhesion Structures
Author(s) -
Teti Anna,
Migliaccio Silvia,
Taranta Anna,
Bernardini Silvia,
De Rossi Giulio,
Luciani Matteo,
Iacobini Metello,
De Felice Lidia,
Boldrini Renata,
Bosman Cesare,
Corsi Alessandro,
Bianco Paolo
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.12.2107
Subject(s) - osteoclast , bone resorption , calcitonin receptor , podosome , osteopetrosis , vitronectin , multinucleate , microbiology and biotechnology , stromal cell , acid phosphatase , population , chemistry , calcitonin , medicine , endocrinology , biology , integrin , receptor , cell , biochemistry , calcitonin gene related peptide , cytoskeleton , neuropeptide , enzyme , environmental health
Osteoclasts from a patient affected by osteopetrosis were examined in vivo and in vitro. Iliac crest biopsy revealed an osteosclerotic pattern, with prominent numbers of osteoclasts noted for hypernuclearity and incomplete adherence to the bone surface. A population comprising tartrate‐resistant acid phosphatase (TRAP)‐positive, multinucleated and mononuclear cells, and alkaline phosphatase‐positive stromal fibroblasts was obtained in vitro from bone marrow. Mononuclear TRAP‐positive precursors spontaneously fused in culture to form giant osteoclast‐like cells. These cells expressed the osteoclast marker MMP‐9 and calcitonin receptor, and lacked the macrophage marker, Fc receptor. Expression and distribution of c‐ src , c‐ fms , and CD68, and response to steroid hormones relevant to osteoclast differentiation and function were apparently normal, whereas cell retraction in response to calcitonin was impaired. TRAP‐positive multinucleated cells did not form osteoclast‐specific adhesion structures (clear zone, podosomes, or actin rings). Bone resorption rate was severely reduced in vitro. Focal adhesions and stress fibers were observed en lieu of podosomes and actin rings. Adhesion structures contained low levels of immunoreactive vitronectin receptor, most of this integrin being retained in cytoplasmic vesicles. These data provide the first characterization of abnormal differentiation and function of human osteopetrotic osteoclast‐like cells.