Mone Zaidi

Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study.

SummaryBesides the calcitonin (CT) precursor, the calcitonin gene also encodes another peptide—calcitonin gene-related peptide (CGRP). We have previously reported that CGRP lowers plasma calcium in the rat. In the present study we have evaluated the effect of CGRP on resorption of bone by isolated rat osteoclasts and have compared these effects to those produced by calcitonins from three species (salmon, pig, and human calcitonins). There was a significant inhibition of bone resorption with rat calcitonin gene-related peptide (rCGRP) at a 1000-fold higher dose than that used for human CT. This effect well explains the CT-like effect of CGRP seen in thein vivo rat CT bioassay. Our results suggest that though CGRP may not be involved in the hormonal control of plasma calcium, the peptide may be an important local regulator of bone cell function.

Inhibition of osteoclastic acid phosphatase abolishes bone resorption.

Osteoclastic acid phosphatase is a member of a widely-distributed class of iron-containing proteins with acid phosphatase activity. Antibodies raised against one member of this class cross-react with other members from the same or different species, but not with acid phosphatase isoenzymes of different types. When antibodies to one such protein, porcine uteroferrin, are added to medium in which rat osteoclasts are incubated on devitalised cortical bone, both bone resorption and acid phosphatase activity are markedly inhibited. Furthermore, addition of molybdate (an inhibitor of this class of acid phosphatases) also inhibits both bone resorption and enzyme activity. These observations strongly suggest a functional role for osteoclastic acid phosphatase in bone resorption.

Transient appearance of calcitonin gene-related peptide-like immunoreactive fibers in the developing cerebellum of the rat

A plexus of calcitonin gene-related peptide (CGRP)-containing fibers were transiently found in the developing cerebellum of the rat by means of the indirect immunofluorescent method. CGRP-like immunoreactive fibers appeared in the cerebellum by embryonic day 22. Immunoreactive fibers rapidly increased and these made a dense plexus in the Purkinje cell layer by postnatal day 2. However, only a few if any immunoreactive fibers were seen in the Purkinje cell layer or molecular layer of adult rats.

The Molecular Pharmacology of Osteoporosis

Skeletal remodeling requires a balance between the resorption and formation of bone. Osteoclasts resorb bone, while osteoblasts are bone forming. These two processes are closely coupled but independently regulated by various hormones and cytokines. Osteoporosis is a disease characterized by excess osteoclastic activity compared to osteoblastic activity. Because of excess osteoclastic activity bones become fragile and may fracture, typically in the hip, spine, and wrist. Pharmacological therapy for osteoporosis should be aimed at preventing bone loss, whether the cause is involutional, postmenopausal, or secondary.

Overview: Inhibitors of Bone Resorption and Implications for Therapy

(1992). Overview: Inhibitors of Bone Resorption and Implications for Therapy. Current Opinion on Therapeutic Patents: Vol. 2, No. 10, pp. 1517-1538.

The Cellular and Molecular Aspects of Immunosuppressant Osteoporosis

The advent of immunosuppressant agents that prevent organ rejection and prolong life has revolutionized the field of organ transplantation. However, these drugs possess numerous side effects, including bone loss that results in osteoporosis and fracture. This chapter will focus on the mechanism of action of the major immunosuppressants used clinically. These include glucocorticoids, the calcineurin inhibitors (cyclosporin A [CsA] and tacrolimus [FK506]), rapamycin, and several others, such as azathiaprine and mycophenolate mofetil (MMF). We will describe in vitro and in vivo studies that have elucidated their action on bone.