Inhibitory mechanisms of H<sup>+</sup>‐ATPase inhibitor bafilomycin A<sub>1</sub> and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption

Ohba, Yasuo; Ohba, Tomoko; Sumitani, Koji; Tagami-Kondoh, Kahori; Hiura, Kenji; Miki, Yoshiki; Kakegawa, Hisao; Takano‐Yamamoto, Teruko; Katunuma, Nobuhiko

doi:10.1016/0014-5793(96)00482-6

Cited by 17 publications

(3 citation statements)

References 22 publications

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“…As seen in Figure 2A and 2B, all the acidification blockers at the highest concentrations tested reduced the resorbed bone area dramatically, as expected from the reduced organic and inorganic bone resorption seen in Figure 1 and previous studies [23,40,41,50]. …”

Section: Resultssupporting

confidence: 83%

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Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Neutzsky-Wulff

Sørensen

Kocijancic

et al. 2010

BMC Musculoskelet Disord

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BackgroundNormal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly have secondary effects on bone remodeling, a process which is of importance for the pathogenesis of both osteoporosis and osteoarthritis. We treated human osteoclasts with different inhibitors and characterized their resulting function.MethodsHuman CD14 + monocytes were differentiated into mature osteoclasts using RANKL and M-CSF. The osteoclasts were cultured on bone in the presence or absence of various inhibitors: Inhibitors of acidification (bafilomycin A1, diphyllin, ethoxyzolamide), inhibitors of proteolysis (E64, GM6001), or a bisphosphonate (ibandronate). Osteoclast numbers and bone resorption were monitored by measurements of TRACP activity, the release of calcium, CTX-I and ICTP, as well as by counting resorption pits.ResultsAll inhibitors of acidification were equally potent with respect to inhibition of both organic and inorganic resorption. In contrast, inhibition of proteolysis by E64 potently reduced organic resorption, but only modestly suppressed inorganic resorption. GM6001 alone did not greatly affect bone resorption. However, when GM6001 and E64 were combined, a complete abrogation of organic bone resorption was observed, without a great effect on inorganic resorption. Ibandronate abrogated both organic and inorganic resorption at all concentrations tested [0.3-100 μM], however, this treatment dramatically reduced TRACP activity.ConclusionsWe present evidence highlighting important differences with respect to osteoclast function, when comparing the different types of osteoclast inhibitors. Each class of osteoclast inhibitors will lead to different alterations in osteoclast quality, which secondarily may lead to different bone qualities.

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Section: Resultssupporting

confidence: 83%

“…It catalyzes the conversion of H 2 O and CO 2 into H 2 CO 3 , which then is ionized into H + and HCO 3 - [21-23]. Mutations in CAII can also cause osteopetrosis due to non-functional osteoclasts [21].…”

Section: Introductionmentioning

confidence: 99%

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Neutzsky-Wulff

Sørensen

Kocijancic

et al. 2010

BMC Musculoskelet Disord

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“…This can be explained by the mechanism of action of the active substance in the solution. Specifically, acetazolamide is known to be a potent inhibitor of carbonic anhydrase [4748], an enzyme presents in osteoclasts. This enzyme catalyzes the reaction between carbonic acid and water, leading to the formation of hydrogen ions [49], which are responsible for the decrease in pH in Howship lacunae [49].…”

Section: Reviewmentioning

confidence: 99%

Effect of calcium hydroxide on inflammatory root resorption and ankylosis in replanted teeth compared with other intracanal materials: a review

Jahromi

Motamedi

2019

Restor Dent Endod

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Calcium hydroxide (CH) is the gold-standard intracanal dressing for teeth subjected to traumatic avulsion. A common complication after the replantation of avulsed teeth is root resorption (RR). The current review was conducted to compare the effect of CH with that of other intracanal medications and filling materials on inflammatory RR and replacement RR (ankylosis) in replanted teeth. The PubMed and Scopus databases were searched through June 2018 using specific keywords related to the title of the present article. The materials that were compared to CH were in 2 categories: 1) mineral trioxide aggregate (MTA) and endodontic sealers as permanent filling materials for single-visit treatment, and 2) Ledermix, bisphosphonates, acetazolamide, indomethacin, gallium nitrate, and enamel matrix-derived protein (Emdogain) as intracanal medicaments for multiple-visit management of avulsed teeth prior to the final obturation. MTA can be used as a single-visit root filling material; however, there are limited data on its efficacy due to a lack of clinical trials. Ledermix and acetazolamide were comparable to CH in reducing RR. Emdogain seems to be an interesting material, but the data supporting its use as an intracanal medication remain very limited. The conclusions drawn in this study were limited by the insufficiency of clinical trials.

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Dissolution of poorly crystalline apatite crystals by osteoclasts determined on artificial thin-film apatite

Kim

Woo

et al. 2001

J. Biomed. Mater. Res.

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Poorly crystalline apatite (PCA) crystals introduced into bone tissue should be stable for a definite period before they are dissolved as a result of a host response. In this report, the dissolution of PCA crystals by the action of osteoclasts was studied on artificial thin films. These consisted of PCA crystals having similar crystallographic properties to bone crystals which were developed for assaying the osteoclast activity in vitro. The dissolution of minerals by osteoclasts decreased along with the decreased amount of labile phosphate and hydrogen phosphate domains of apatite crystals, which were caused by the crystal maturation temperature. A profound effect on mineral dissolution by pH in the culture medium was also shown. Low acidity considerably increased mineral dissolution, whereas a slight alkalinity totally blocked mineral dissolution. There was little difference in the mineral dissolution behavior of osteoclasts near the physiologic pH. In addition, it was determined whether mineral dissolution by osteoclasts was dependent on the destruction of the organic matrix. Nocodazole was introduced to inhibit the secretion of hydrolytic enzymes, and acetazolamide was added to inhibit acid production by the osteoclasts. There was no significant change as a result of nocodazole addition on mineral dissolution or by the addition of acetazolamide on degradation of collagen. These results indicate that small changes in the physicochemical properties of apatite crystals can decrease resorption by osteoclasts, which can be highly activated at low pH. These results also suggest that mineral dissolution and organic degradation by osteoclasts are self-regulating.

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Inhibitory mechanisms of H⁺‐ATPase inhibitor bafilomycin A₁ and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption

Cited by 17 publications

References 22 publications

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Effect of calcium hydroxide on inflammatory root resorption and ankylosis in replanted teeth compared with other intracanal materials: a review

Dissolution of poorly crystalline apatite crystals by osteoclasts determined on artificial thin-film apatite

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Inhibitory mechanisms of H+‐ATPase inhibitor bafilomycin A1 and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption

Cited by 17 publications

References 22 publications

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

Effect of calcium hydroxide on inflammatory root resorption and ankylosis in replanted teeth compared with other intracanal materials: a review

Dissolution of poorly crystalline apatite crystals by osteoclasts determined on artificial thin-film apatite

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Inhibitory mechanisms of H⁺‐ATPase inhibitor bafilomycin A₁ and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption