Osteoclasts have been defined as calcitonin (CT) and vitronectin (VN) receptor (R) positive, and CD14-, CD11b- and CD11c-negative cells which resorb bone. The aim of this study was to identify the phenotype of the osteoclast precursor. Osteoclasts were generated by co-culturing peripheral blood mononuclear cells (PBMNCS) with the rat osteoblastic UMR 106 cell line. On days 2-4 at least 80% of CTR-positive cells co-expressed CD14, CD11b and CD11c (monocyte markers), but by day 14 < 3.3% expressed these markers. Selection of CD14-positive monocytes from PBMNCS enhanced osteoclastic bone resorption 2-4-fold compared to unfractionated PBMNCS. This study demonstrates that osteoclasts derive largely from CD14-positive monocytes.

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Summary. Osteoclasts utilize avb3 integrin adhesion to bone matrix during bone resorption. We have generated osteoclasts from the peripheral blood of Iraqi-Jewish patients with Glanzmann thrombasthenia (GT) who are completely deficient in b3 integrin and exhibit a haemorrhagic diathesis resulting from the absence of platelet aIIbb3. We show that, in contrast to osteoclasts generated from normal subjects or patients with aIIb integrin deficiency, GT osteoclasts lack avb3. These osteoclasts exhibited a two-to fourfold increase in a2 and b1 integrin expression, whereas other av integrins, including avb5, were not significantly affected. An accompanying decrease in bone resorption was observed, with 44% and 59% declines in pit number and depth, respectively, and resorption lacunae showed abnormal morphology on scanning electron microscopy. However, osteoclasts from GT developed in similar numbers to controls and exhibited an otherwise 'normal' phenotype. We conclude that the observed rise in a2b1 expression compensates for the chronic genetic deficiency of avb3 in osteoclasts from patients with GT and is sufficient to enable bone resorption to proceed, albeit to a submaximal extent. This explains why Iraqi-Jewish patients with GT do not have osteopetrosis.

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