A Novel Osteoblast-derived C-type Lectin That Inhibits Osteoclast Formation

Zhou, Hong; Kartsogiannis, Vicky; Hu, Yun; Elliott, Jan; Quinn, J; McKinstry, William J.; Gillespie, Matthew T.; Ng, Kong Wah

doi:10.1074/jbc.m011554200

Cited by 67 publications

(83 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that Clr7 is not a pseudogene as suggested by Hao et al [6], but a fully functional gene. Of the remaining members, Clr5 has been reported previously [23,25]. We have also cloned Clr10, but have not been able to reliably express it on the cell surface (our unpublished data).…”

Section: Discussionmentioning

confidence: 92%

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

et al. 2009

View full text Add to dashboard Cite

A major subset of non-alloreactive NK cells in PVG strain rats is generally low in Ly49 receptors, but expresses the rat NKR-P1B PVG receptor (previously termed NKR-P1C). The NKR-P1B 1 NK subset is inhibited by a non-polymorphic target cell ligand, which we have shown here to be a C-type lectin-related molecule (Clr). Clr11 ligates two divergent NKR-P1B alleles as judged by an NFAT-driven reporter assay, and inhibits NK-cell cytotoxicity of NKR-P1B 1 NK cells. Clr11 also interacts with the prototypic NKR-P1A receptor and exerts a stimulatory influence on NK lysis. NKR-P1A and B are encoded by adjacent genes in the proximal part of the NK gene complex and show close sequence homology in their extracellular region. They diverge from another pair, NKR-P1F and -G, which is encoded by a second, distal Nkrp1 gene cluster. NKR-P1F and -G bind an overlapping panel of Clr ligands, but not Clr11. Rat Clr molecules appear to be constitutively expressed by hematopoietic cells; expression in tumor cell lines is more variable. The data show the existence of two phylogenetic groups of NKR-P1 molecules, which demonstrate conservation of ligand-binding properties independent of signaling function.Key words: Cytotoxicity . NK cells . Receptor . Rodent Introduction NK cells express several families of killer cell lectin-like receptors (KLR). These are type II transmembrane proteins encoded by the NK gene complex (NKC), which is located on chromosome 4 in the rat [1,2]. The NKR-P1 molecules (KLRB or CD161) were among the first KLR to be characterized, but their function long remained elusive [3][4][5]. Although the NKR-P1 family has expanded to include both activating and inhibitory members in rodents, it consists of only one member in several other mammalian species, including in human [6]. The nature of their ligands has been controversial [7,8], but it has recently been shown that members of another KLR-related receptor family, the C-type lectin-related (Clr) molecules [9], also termed C-type lectin 2D (CLEC2D), can act as ligands for certain NKR-P1 molecules [10,11]. The Clr gene family also shows considerable expansion in rodents and the Clr genes are interspersed with the Nkrp1 genes in the proximal (centromeric) part of the NKC. A recent analysis concluded that there are 11 Clr/Clec2d genes in the rat BN strain genome, which were numbered consecutively from proximal to distal. One of these (Clr8) is most likely only a gene fragment, which could have been excluded, but we will nevertheless adhere to the Clr numbering suggested by Hao et al. [6].In the mouse, the inhibitory NKR-P1B and -D receptors both bind Clrb (also termed Ocil). Clrb is constitutively expressed by hematopoietic cells and inhibits cytolytic activity of NKR-P1B/ D-expressing NK cells [10,11]. The activating NKR-P1F receptor has been shown to bind another Clr molecule, Clrg, by the use of a reporter assay and soluble recombinant proteins [11] functional consequence of this interaction remains obscure. In human, the NKR-P1A receptor binds a Clr orthologue term...

show abstract

Section: Discussionmentioning

confidence: 92%

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This suggests that a site independent of CRD on galectin-3 interacts with receptor-like molecules on cell surface of osteoclast precursors to inhibit osteoclast formation. Similarly, it has been reported that the osteoclast inhibitory lectin, a C-type lectin, inhibits osteoclast formation 42,43 without acting through their carbohydrate recognition moieties. 44 As the N-terminal portions bearing no glycan-binding sites have unique properties to bind nonglycan ligands, 45 this portion of galectin-3 is likely to contribute to the suppression of osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats

Kukita

Teramachi

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

Galectin-3 is a b-galactoside-binding animal lectin having pleiotropic effects on cell growth, differentiation, and apoptosis. This lectin has been shown to be involved in phagocytosis by macrophages and in inflammation. Here we investigated an involvement of galectin-3 in the regulatory process of inflammatory bone resorption in rats with adjuvant-induced arthritis (AA rats) accompanying severe bone destruction in the ankle joints. The protein level of galectin-3 in the ankle-joint extracts was markedly augmented at week 3 after adjuvant injection, at the time when severe bone destruction was observed. Immunohistochemical analysis revealed an extremely high expression of galectin-3 in macrophages and granulocytes infiltrated in the area of severe bone destruction. To estimate the role of galectin-3 in osteoclastogenesis and osteoclastic bone resorption, recombinant galectin-3 was added to in vitro culture systems. Galectin-3 markedly inhibited the formation of osteoclasts in cultures of murine osteoclast precursor cell line as well as in rat bone marrow culture systems. This inhibition was not observed by heat-inactivated galectin-3 or by galectin-7. Although recombinant galectin-3 did not affect signaling through mitogen-activated protein kinase (MAPK) or nuclear factor-kB (NF-kB), it specifically suppressed the induction of nuclear factor of activated T-cells c1 (NFATc1). Galectin-3 significantly inhibited dentine resorption by mature osteoclasts in vitro. Furthermore, in vivo studies clearly showed a significant suppression of bone destruction and osteoclast recruitment accompanying arthritis, when galectin-3 was injected into the cavity of ankle joint of AA rats. Thus, abundant galectin-3 observed in the area of severe bone destruction may act as a negative regulator for the upregulated osteoclastogenesis accompanying inflammation to prevent excess bone destruction.

show abstract

“…OCIL is a member of a small family of related proteins that includes murine OCILrP1 and murine OCILrP2 (also called CLR-g) (6), and one human homolog has also been identified (2). We have previously shown that the soluble recombinant C-type lectin domains of each of these molecules inhibit osteoclast formation with similar potency (1,2,6).…”

mentioning

confidence: 99%

“…acts as an inhibitor of osteoclastogenesis in vitro (1,2). Originally identified in osteoblasts, OCIL mRNA levels are regulated by many osteotropic hormones and cytokines.…”

mentioning

confidence: 99%

“…Originally identified in osteoblasts, OCIL mRNA levels are regulated by many osteotropic hormones and cytokines. Murine OCIL (also known as CLR-b for C-type lectin-related molecule-b) (3) is widely expressed in most tissues, notably in epithelial and mesenchymal cells, but also in dendritic, macrophage, and lymphocyte populations (1,4,5). OCIL is a member of a small family of related proteins that includes murine OCILrP1 and murine OCILrP2 (also called CLR-g) (6), and one human homolog has also been identified (2).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Gange

Quinn

Zhou

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Osteoclast inhibitory lectin (OCIL) is a membranebound C-type lectin that blocks osteoclast differentiation and, via binding to its cognate receptor NKRP1D, inhibits natural killer cell-mediated cytotoxicity. OCIL is a member of the natural killer cell receptor C-type lectin group that includes CD69 and NKRP1D. We investigated carbohydrate binding of soluble recombinant human and mouse OCIL in enzyme-linked immunosorbent assay-based assays. OCIL bound immobilized high molecular weight sulfated glycosaminoglycans, including fucoidan, -carrageenan, and dextran sulfate, but not unsulfated dextran or sialated hyaluronic acid. Carbohydrate binding was Ca 2؉ -independent. Binding of immobilized low molecular weight glycosaminoglycans, including chondroitin sulfate (A, B, and C forms) and heparin, was not observed. However, the soluble forms of these low molecular weight glycosaminoglycans competed for OCIL binding of immobilized fucoidan (as did soluble fucoidan, dextran sulfate, and -carrageenan), indicating that OCIL does recognize these carbohydrates. Inhibition constants for chondroitin sulfate A and heparin binding were 380 and 5 nM, respectively. Immobilized and soluble monosaccharides did not bind OCIL. The presence of saturating levels of fucoidan, dextran sulfate, and -carrageenan did not affect OCIL inhibition of osteoclast formation. The fucoidan-binding lectins Ulex europaeus agglutinin I and Anguilla anguilla agglutinin did not block osteoclast formation or affect the inhibitory action of OCIL. Although the osteoclast inhibitory action of OCIL is independent of sugar recognition, we have found that OCIL, a lectin widely distributed, but notably localized in bone, skin, and other connective tissues, binds a range of physiologically important glycosaminoglycans, and this property may modulate OCIL actions upon other cells.

show abstract

A Novel Osteoblast-derived C-type Lectin That Inhibits Osteoclast Formation

Cited by 67 publications

References 60 publications

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats

Characterization of Sugar Binding by Osteoclast Inhibitory Lectin

Contact Info

Product

Resources

About