RGD Reference Report - CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption. - Rat Genome Database

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CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

Authors: Sun, L  Adebanjo, OA  Moonga, BS  Corisdeo, S  Anandatheerthavarada, HK  Biswas, G  Arakawa, T  Hakeda, Y  Koval, A  Sodam, B  Bevis, PJ  Moser, AJ  Lai, FA  Epstein, S  Troen, BR  Kumegawa, M  Zaidi, M 
Citation: Sun L, etal., J Cell Biol. 1999 Sep 6;146(5):1161-72.
RGD ID: 2307268
Pubmed: PMID:10477767   (View Abstract at PubMed)
PMCID: PMC2169484   (View Article at PubMed Central)

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cd38Ratnegative regulation of bone resorption  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd38  (CD38 molecule)


Additional Information