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

Abstract

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.

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

“…22 Five-week-old female Lewis rats were anesthetized with diethyl ether and were intradermally injected at the base of the tail with complete Freund adjuvant (CFA) containing 25 mg/kg heat-killed M. butyricum (Difco Laboratories) suspended in mineral oil. For the control experiments, rat were injected with mineral oil alone.…”

“…22 The total proteins were extracted in the lysis buffer containing 1% Triton X-100, 0.5% NP-40, 150 mM NaCl, 50 mM Tris-HCl (pH 7.4), 1 mM NaF, 1 mM Na 3 VO 4 , 1 mM phenylmethylsulfonyl fluoride, and protease inhibitor cocktail (Sigma, St Louis, MO, USA). Cell lysates, containing equal amounts of proteins, were subjected to 10% SDS-PAGE and transferred to nitrocellulose membranes.…”

Synergistic and Additive Effects of Modified Citrus Pectin With Two Polybotanical Compounds, in the Suppression of Invasive Behavior of Human Breast and Prostate Cancer Cells

“…26,27 Interestingly, Chen et al 28 demonstrated AP-1 and NF-κB inhibition by citrus pectin in activated macrophages, but this effect was associated with the suppression of LPS/TLR-4 signaling. On the other hand, galectin-3 did not affect signaling through NF-κB in macrophages, 29 whereas galectin-3 activated NF-κB in colonic epithelial lamina propria fibroblasts and rheumatoid arthritis synovial fibroblasts. 30,31 Since nuclear phosphorylated galectin-3 also interacts with other transcription factors (eg, AP-1, TTF-1, SP1, and CRE) and controls the expression of cancer-related genes, 32 it is possible that MCP inhibits the interactions between galectin-3 and NF-κB or AP-1, which results in the inhibition of the expression and secretion of uPA.…”

Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including <i>O</i>-GlcNAcylation

“…13) In addition, sugar-binding proteins such as siglec, which interact with sialic acid, and galectins, which interact with Galβ1-4GlcNAc, also have important roles in osteoclastogenesis. [14][15][16][17][18][19] Therefore, in order to clarify the potential for GlcN-mediated glycosylation modification, we investigated the effect of GlcN treatment on the pattern of glycosylation using lectin blotting of cell extracts with SSA, MAM, RCA120, PHA-E 4 , Con A, and LCA, which mainly recognize α2,6-linked sialic acid, α2,3-linked sialic acid, Galβ1-4GlcNAc, bisecting GlcNAc, high mannose type Nglycan, and N-glycan core modified with fucose, respectively (Figs. 2B-G).…”