Osteoclast inhibitory lectin, an immune cell product that is required for normal bone physiology in vivo.
Osteoclast inhibitory lectin (OCIL or clrb) is a member of the natural killer cell C-type lectins that have a described role mostly in autoimmune cell function. OCIL was originally identified as an osteoblast-derived inhibitor of osteoclast formation in vitro. To determine the physiological function(s) of OCIL, we generated ocil(-/-) mice. These mice appeared healthy and were fertile, with no apparent immune function defect, and phenotypic abnormalities were limited to bone. Histomorphometric analysis revealed a significantly lower tibial trabecular bone volume and trabecular number in the 10- and 16-week-old male ocil(-/-) mice compared with wild type mice. Furthermore, ocil(-/-) mice showed reduced bone formation rate in the 10-week-old females and 16-week-old males while Static markers of bone formation showed no significant changes in male or female ocil(-/-) mice. Examination of bone resorption markers in the long bones of ocil(-/-) mice indicated a transient increase in osteoclast number per unit bone perimeter. Enhanced osteoclast formation was also observed when either bone marrow or splenic cultures were generated in vitro from ocil(-/-) mice relative to wild type control cultures. Loss of ocil therefore resulted in osteopenia in adult mice primarily as a result of increased osteoclast formation and/or decreased bone formation. The enhanced osteoclastic activity led to elevated serum calcium levels, which resulted in the suppression of circulating parathyroid hormone in 10-week-old ocil(-/-) mice compared with wild type control mice. Collectively, our data suggest that OCIL is a physiological negative regulator of bone.
Kartsogiannis
Vicky
V
St. Vincent's Institute, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
Sims
Natalie A
NA
Quinn
Julian M W
JM
Ly
Chi
C
Cipetic
Mirijana
M
Poulton
Ingrid J
IJ
Walker
Emma C
EC
Saleh
Hasnawati
H
McGregor
Narelle E
NE
Wallace
Morgan E
ME
Smyth
Mark J
MJ
Martin
T John
TJ
Zhou
Hong
H
Ng
Kong Wah
KW
Gillespie
Matthew T
MT
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000235:genetics; D001862:Bone Resorption / Q000097:blood / Q000235:genetics; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000502:physiology; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D013977:Tibia / Q000378:metabolism*
D037181:Lectins, C-Type; D008565:Membrane Proteins; C429003:Ocil protein, mouse; D002118:Calcium
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