Biochemical and Biophysical Research Communications
Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival
Section snippets
Materials and methods
Drugs and chemicals. Bafilomycin A1 was purchased from Calbiochem. Ryanodine was purchased from Biomol. The culture medium was from Life Technologies. The remaining chemicals were from Sigma–Aldrich, unless otherwise specified.
Cell culture. The CD14+ isolation was performed as previously described [18]. Briefly, the monocytes were isolated from peripheral blood by centrifugation on a Ficoll-Paque gradient (Amersham Pharmacia) and magnetically sorted using a CD14+ magnetic bead isolation kit
Inhibition of acidification promotes osteoclast survival on calcified bones, but not decalcified bones
Patients with defective acidification of the resorption lacuna have increased numbers of non-resorbing osteoclasts [20]. We investigated the effect of inhibition of the V-ATPase with respect to survival of osteoclasts seeded on calcified and decalcified bone slices. We found that bafilomycin at 20 nM inhibited bone resorption of calcified bone completely (Fig. 1A) and that it augmented osteoclast survival compared to non-treated osteoclasts by 250–300% (p < 0.001) on day 7 and 11, examined by
Discussion
By using a novel approach focusing on the role of the inorganic phase of bone on osteoclast survival, we described that osteoclast life span is regulated by dissolution of the inorganic matrix leading to Ca2+ release, which subsequently induces apoptosis of the osteoclasts, and thereby controls the resorptive activity of the cells. These results explain the increased numbers of osteoclast seen in osteopetrotic patients with defective acidification of the resorption lacunae [20], [22].
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Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts
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Lentiviral gene transfer of TCIRG1 into peripheral blood CD34<sup>+</sup> cells restores osteoclast function in infantile malignant osteopetrosis
2013, BoneCitation Excerpt :This clearly establishes that the introduction of non-mutated TCIRG1 into IMO osteoclasts restores their ability to acidify the resorption lacunae and resorb bone in vitro. Furthermore, in the IMO cells the TRACP levels are increased, a phenomenon which previously has been shown to be related to increased survival of the osteoclasts due to their lowered resorption activity [21,25,26]. Importantly, this process is not specific to lack of TCIRG1 as it is also observed in c-src, cathepsin K and ClC-7 deficient osteoclasts [4,27–30].
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
2012, BoneCitation Excerpt :An interesting aspect in relation to the data from osteoclasts on different matrices is whether calcium in itself is part of the anabolic signal from osteoclasts to osteoblasts. Calcium is known to reduce osteoclast survival [55], and could also be a part of induction of new bone formation [57], although a direct link between calcium released during resorption and bone formation remains to be proven. On the other hand we also observed that diphyllin and E64 reduced the anabolic potential of osteoclasts by similar amounts, which could indicate that calcium is not a major player, as E64 reduces calcium release only by 40% [47].
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2010, Developmental Biology