Amylin inhibits bone resorption by a direct effect on the motility of rat osteoclasts

AS Alam, BS Moonga, PJ Bevis, CL Huang, M. Zaidi

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Abstract

We have performed a set of independent studies on the effects of the circulating pancreatic polypeptide, amylin, on rat osteoclast function, in vitro. Time‐lapse video observations, measuring cell protrusions and retraction, showed that 250 nmol l‐1 amylin or 250 nmol l‐1 beta‐calcitonin gene‐related peptide (beta‐CGRP) inhibited osteoclast motility (quiescence or Q effect). Both amylin and beta‐CGRP produced inhibitory responses with a significant first‐order regression over time (half‐times, 19 and 28 min respectively). In contrast, 250 nmol l‐1 amylin or 250 nmol l‐1 beta‐CGRP produced no change of osteoclast spread area, whilst 300 pmol l‐1 calcitonin (CT) application resulted in cell retraction (R effect). Forskolin (10 mumol l‐1) mimicked amylin and CGRP in inhibiting osteoclast motility (half‐time, 8.6 min), and similarly lacked an effect on cell spread area. Neither amylin nor beta‐CGRP (62.5–1250 nmol l‐1) elevated cytosolic free calcium levels ([Ca2+]i) in single osteoclasts whilst 300 pmol l‐1 salmon calcitonin (sCT) produced a rapid phasic elevation of [Ca2+]i, confirming previous results with asusuberic (1‐7) eel calcitonin. The osteoclast‐bone resorption assay revealed the following potency difference in direct comparison of the area of resorption per bone slice: beta‐CGRP/amylin, 0.1; sCT/amylin, 800 and human CT/amylin, 12. The potency of deamidated amylin approached that of beta‐CGRP. Assay precision ranged between 0.3 and 0.8. Amylin (250 nmol l‐1) also significantly (P < 0.05) reduced supernatant (tartrate‐resistant) acid phosphatase in the bone‐osteoclast cultures. These measures independently indicate an effect of amylin on osteoclast motility through mechanisms distinct from those of calcitonin, possibly through different selectivities for receptor subtypes, the cyclic AMP‐linked 'amylin subtype' and the [Ca2+]i‐linked 'calcitonin subtype'.

Original languageEnglish
Pages (from-to)183-196
Number of pages14
JournalExperimental Physiology
Volume78
Issue number2
DOIs
StatePublished - 1 Mar 1993

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