Osteoclast ultrastructure in Paget’s disease

Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease.

“…These observations are consistent with ultrastructural studies of pagetic bone. Intranuclear viral inclusions have only been reported in mature osteoclasts and not in mononuclear cells (7)(8)(9)(10). Since MNC formed in marrow cultures are formed from mononuclear precursors, we expected that MNC formed in vitro from Paget's marrow might lack viral nuclear inclu- sions.…”

“…This conclusion is based on the following observations: (a) Morphologic studies have demonstrated that abnormal osteoclasts are present in pagetic bone (5,6). These osteoclasts are enormous in size (average number of nuclei 20, compared with three to four for normal osteoclasts) and have greatly increased numbers of folds in their cytoplasmic membranes, reflecting their abnormally increased surface activity and motility (7). (b) Viral nuclear inclusions, viral antigens and viral transcripts have been reported in these osteoclasts (8)(9)(10)(11)(12)(13)(14), suggesting a possible viral etiology for Paget's disease.…”

Bone tissue in paget's disease of bone ultrastructure and immunocytology

“…In comparison to normal cells of this type (21,22,24) they are abnormally large and the number of nuclei considerably increased. The appearance of the mitochondria, the presence of innumerable vesicles near the nuclear and the cytoplasmic membrane, the abundance of glycogen particles are all signs of metabolic disorders in the osteoclasts found in Paget's disease (8,34,35). Similarly, the presence of multiple basal bodies and the aspect of the cell membrane infolding suggest an abnormal increase in the surface activity and the motility of these cells (8,21,36,37).…”

Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

“…The rapid, excessive, focal new bone deposition in PD results in woven bone that is much weaker, can bow and cause bone deformity, fracture, skull thickening, bone pain, secondary osteoarthritis, and nerve root compression (2). The primary cellular abnormality in PD resides in the osteoclast (OCL) (3). OCLs are increased in number and size and express a pagetic phenotype that distinguishes them from normal OCLs (4), including hypermultinucleation, increased TAF12 levels (a coactivator of VDRmediated transcription), and increased 1,25-(OH) 2 D 3 and RANKL responsivity (5)(6)(7).…”