Osteoclast inhibitory lectin, a family of new osteoclast inhibitors.
We have identified two novel type II membrane-bound C-lectins, designated mOCILrP1 and mOCILrP2, of 218 and 217 amino acids, respectively, that share substantial identity with the murine osteoclast inhibitory lectin (OCIL). The extracellular domains of mOCILrP1 and mOCILrP2 share 83 and 75% identity, respectively, with the extracellular domain of mOCIL. When the extracellular domains were expressed as recombinant proteins, each inhibited osteoclast formation in murine bone marrow cultures treated with M-CSF and RANKL with similar potencies to mOCIL (IC(50) of 0.2 ng/ml). Distinct but highly related genes encoded the three OCIL family members, with mOCIL and mOCILrP2 controlled by an inverted TATA promoter, and mOCILrP1 by a TTAAAA promoter. However only mOCIL was robustly regulated by calciotropic agents, while mOCILrP1 was not expressed, and mOCILrP2 was constitutively expressed in osteoblasts. Immunohistochemistry using antipeptide antibodies to the intracellular domain of mOCILrP1/mOCILrP2 and to mOCIL demonstrated that mOCIL and mOCILrP1/mOCILrP2 were concordantly expressed in osteoblasts, chondrocytes, and in extraskeletal tissues. Further, their cellular distribution was identical to that of RANKL. The identification of three distinct genes that were functionally related implies redundancy for OCIL, and their concordant expression with that of RANKL suggests that the RANKL:OPG axis may be further influenced by OCIL family members.
Zhou
Hong
H
St. Vincent's Institute of Medical Research, The University of Melbourne, St. Vincent's Hospital, Fitzroy, 3065, Australia.
Kartsogiannis
Vicky
V
Quinn
Julian M W
JM
Ly
Chi
C
Gange
Christine
C
Elliott
Jan
J
Ng
Kong Wah
KW
Gillespie
Matthew T
MT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D017931:DNA Primers; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; C470572:Dcl1 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; C470571:Ocilrp1 protein, mouse; D012333:RNA, Messenger; D004247:DNA