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

<p>Abstract</p> <p>Background</p> <p>Normal 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.</p> <p>Methods</p> <p>Human 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.</p> <p>Results</p> <p>All 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.</p> <p>Conclusions</p> <p>We 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.</p

What drives the distribution in nature of 3T vs. 2M(1) polytype in muscovites and phengites? A general assessment based on new data from metamorphic and igneous granitoid rocks

Petrologic, chemical, and polytype data are presented for dioctahedral potassic micas from K-feldspar-bearing metamorphic and igneous rocks of acidic composition unaffected by high-pressure (HP) conditions. The paper aims to demonstrate that: (1) under non-HP conditions, in both metamorphic and igneous plutonic environments, a given bulk-rock compositional constraint imposes a more or less marked phengitic composition to dioctahedral potassic mica; and (2) this muscovite crystallizes as 2M1, notwithstanding its phengitic composition. The samples (157 in number) are from widespread provenances. We conclude that the growth of 3T polytype of muscovite is not a function of mica composition. This is consistent with the recent crystallographic knowledge on polytypism, cation ordering, elastic properties, and structural deformational mechanisms of muscovite, which address the stabilization of 3T with pressure. Keywords: Muscovite, phengite, celadonitic substitution, polytypism, 2M1, 3T, pressure-polytype relationship, mica chemistry, polytype relationship, petrologic mineralog

Single-crystal X-ray studies of trioctahedral micas coexisting with dioctahedral micas in metamorphic sequences from Western Maine

A crystal chemical study of thirteen biotite (twelve of 1M polytype and one of 2M1 polytype) and four muscovite samples were made. The biotite, coexists with the muscovite. Samples are from metamorphic terrains and from granitic and granodioritic bodies occurring in three areas of western Maine. The metamorphic mineral zones identified by mineral compatibilities are, for increasing metamorphic grade, the Lower Sillimanite Zone (LSZ), the Upper Sillimanite Zone (USZ) and the K-feldspar + Sillimanite Zone (K+SZ). The muscovite composition clusters near ideal muscovite and displays a small celadonite substitution and a small, but variable paragonite substitution. The biotite composition displays a ratio [vi]Mg2+ / [vi](Mg2+ + Fe2+) ranging from 0.26 to 0.54 and significant octahedral Al content from 0.48 to 0.72 apfu in metamorphic biotite samples and from 0.51 to 0.67 in those from granites).In trioctahedral micas from western Maine and especially in those with graphite, there is a greater number of interlayer vacancies than in common micas. Interlayer vacancies have an increase in interlayer cation – basal oxygen atom distances and a decrease in tetrahedral flattening angle tau, thus suggesting a reduced interlayer charge. With a few exceptions, tetrahedral rotation angle alpha is related to crystallization temperature. In particular alpha decreases with a temperature increase, and alpha is also related to octahedral chemical substitutions. Results tentatively suggest, for micas from metamorphic environments, a direct influence of genetic parameters (T and fO2) on mica crystal structure, and not just chemical composition