New model for bone resorption study in vitro: Human osteoclast-like cells from giant cell tumors of bone

Osteoclasts are polarized cells with a basolateral and an apical membrane exposed to different extracellular Ca2+ ([Ca2+]o) and H+ (pHe) concentrations. Osteoclast bone resorption is inhibited in vitro by increases of [Ca2+]o slightly above physiological levels, detected by a [Ca2+]o sensing causing elevations of the intracellular signal, [Ca2+]i. Nevertheless, during bone resorption the apical membrane is exposed to [Ca2+]o severalfold higher than physiological without apparent inhibition of osteoclast functions. Because pHe facing the apical membrane is acidic, in this single-cell [Ca2+]i and intracellular pH study we addressed the question of whether the responses of human osteoclast-like cells from a giant cell tumor of bone to elevated [Ca2+]o are altered by reducing pHe. We first observed that low pHe stimulated Ca2+ efflux and cell acidification. We then demonstrated that the amplitude of the [Ca2+]o-dependent [Ca2+]i "spikes" is downregulated by low pHe, with approximately 70-fold higher [Ca2+]o required to induce significant responses at pHe 6.0 compared with pHe 7.4. Similar downregulation was observed in authentic freshly isolated rat osteoclasts. Finally, we observed that occupancy of the [Ca2+]o sensing by Ca2+ prompted rapid and transient cell acidification partially counteracted by a Na(+)-dependent amiloride derivative-sensitive H+ transport. These results demonstrate that the cascade of events triggered by activation of the [Ca2+]o sensing is affected by environmental pH and in turn influences cellular H+ transport. Such pH-related features of the [Ca2+] o sensing mechanism might be relevant for the regulation of osteoclast-like function.

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Faculty Opinions recommendation of Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7679956.7994054 ◽

2011 ◽

Author(s):

Maria Luisa Brandi ◽

Gemma Marcucci

Keyword(s):

Giant Cell ◽

Bone Destruction ◽

Giant Cell Tumors ◽

Tumors Of Bone

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Giant Cell Tumor of the Talar Neck

Journal of the American Podiatric Medical Association ◽

10.7547/0970225 ◽

2007 ◽

Vol 97 (3) ◽

pp. 225-228 ◽

Cited By ~ 7

Author(s):

Hakan Selek ◽

Hamza Özer ◽

Sacit Turanli ◽

Özlem Erdem

Keyword(s):

Giant Cell Tumor ◽

Giant Cell ◽

Clinical Signs ◽

Cell Tumor ◽

Giant Cell Tumors ◽

Radiographic Appearance ◽

Aneurysmal Bone Cysts ◽

Tumors Of Bone ◽

Brown Tumors ◽

Small Bones

We describe a patient with a giant cell tumor in the talar head and neck of the left foot who was diagnosed as having osteochondritis dissecans and treated with arthroscopic drilling in this same location 3 years earlier. Giant cell tumors can be confused with several conditions, including giant cell reparative granulomas, brown tumors, and aneurysmal bone cysts. Giant cell tumors of bone typically occur in the epiphysis of long bones, including the distal femur and proximal tibia. They are uncommonly found in the small bones of the foot or ankle, and talar involvement is rare. Despite this rarity, the radiographic appearance and clinical signs of talar lesions should be considered in the differential diagnosis of nontraumatic conditions in the foot. (J Am Podiatr Med Assoc 97(3): 225–228, 2007)

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