Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoclasts are derived from hematopoietic stem cells, but details about their precursor are still obscure. We present here a mouse macrophage cell line, BDM-1 cells, that showed a high potential to differentiate into osteoclast-like multinucleate cells (MNCs) when cocultured with primary osteoblasts for 14 days in the presence of 10(-8) M 1 alpha,25-dihydroxyvitamin D3. These MNCs had tartrate-resistant acid phosphatase (TRAP) activity and strong ability to resorb dentine. In this culture system, 10(-10)-10(-8) M 12-O-tetradecanoylphorbol-13-acetate stimulated the formation of TRAP-positive MNCs, whereas salmon calcitonin inhibited it. Time-course effect studies showed that 12-O-tetradecanoylphorbol-13-acetate had an effect on the late phase of osteoclast differentiation but not on precursor proliferation. By immunocytochemical staining, all BDM-1 cells expressed Mac-1, Mac-2, and MOMA-2 antigens, and a large number of them expressed F4/80 antigen, but the rest of them were negative for this antigen. To select subclones able to differentiate into TRAP-positive MNCs, we sought to isolate several subclones from BDM-1 cells by mean of different specificity for F4/80 antigen expression. TRAP-positive MNCs were not generated from F4/80-positive subclones, but were obtained from subclones containing F4/80-negative cells. These results suggest that an F4/80-negative macrophage subpopulation is responsible for the differentiation of this cell line into osteoclasts.
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PMID:In vitro differentiation of the murine macrophage cell line BDM-1 into osteoclast-like cells. 766 46

Osteoclast deficiency in op/op mice is cured by a single injection of 5 micrograms recombinant human macrophage colony-stimulating factor (rhM-CSF). In this study, we found that mouse osteoclasts are positive for Mac-2 antigen, but not for F4/80, MOMA-2, Mac-1, or BM8 antigen. By using F4/80 and MOMA-2 monoclonal antibodies, we confirmed the absence of mature macrophages in the femora of op/op mice and found that multiple injections of rhM-CSF are required for the recruitment of macrophages in the bones. After a single rhM-CSF injection, we found Mac-2 positive mononuclear cells in the femora of op/op mice. The time course of the appearance of Mac-2-positive cells was very similar to that of tartrate-resistant acid phosphatase (TRAP)-positive cells. In bone sections prepared from the mutant mice that received rhM-CSF 3 days earlier, 91% of the TRAP-positive mononuclear cells were also positive for Mac-2 antigen. These results demonstrate the expression of Mac-2 antigen in preosteoclasts. The antigen was detected on the plasma membrane of preosteoclasts, as well as in their cytoplasm and nucleus, and in the extracellular matrix in the space between the cells and bone. Since Mac-2 is a galactose-specific lectin, a potential role of the lectin in cell-cell and cell-matrix adhesion during osteoclast differentiation is suggested.
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PMID:Expression of Mac-2 antigen in the preosteoclast and osteoclast identified in the op/op mouse injected with macrophage colony-stimulating factor. 807 62

We previously demonstrated that osteoclast-like multinucleated cells were formed within 6 days in cocultures of mouse osteoblastic cells and spleen cells in response to 1 alpha,25-dihydroxyvitamin D3[1 alpha,25(OH)2D3] which was added together with hydroxyurea on Days 4-6 (final 2 days of the 6-day coculture period). Using this coculture system, chronological changes of macrophage-associated phenotypes such as nonspecific esterase (NSE) and antigens to Mac-1, Mac-2, and F4/80 were examined in postmitotic osteoclast precursors during differentiation into osteoclasts induced by 1 alpha,25(OH)2D3 (10 nM) added on Day 4. Osteoclast differentiation was assessed by examining expression of calcitonin receptors (CTRs) by autoradiography using 125I-labeled salmon CT. CTRs were first detected on small mononuclear cells within 12 hr after adding 1 alpha,25(OH)2D3. The number of CTR-positive mononuclear cells attained a maximum at 24 hr and decreased thereafter. CTR-positive multinucleated cells were first observed at 24 hr and reached a maximum population at 48 hr. All CTR-positive cells showed tartrate-resistant acid phosphatase activity (a marker enzyme of osteoclasts). Most of the CTR-positive mononuclear cells which appeared at 12 hr were positive for NSE and antigens to Mac-1 and Mac-2, but negative for F4/80 antigen. The proportion of CTR-positive cells expressing NSE and Mac-1 to total CTR-positive mononuclear cells decreased time dependently. Like authentic osteoclasts, CTR-positive multinucleated cells were negative for NSE and antigens to Mac-1 and F4/80, but positive for Mac-2. These results indicate that postmitotic osteoclast precursors are mononuclear phagocytes with macrophage-associated phenotypes, some of which disappear rapidly during their differentiation into osteoclasts.
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PMID:Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes. 817 77

Osteoclasts are formed in cocultures of mouse calvarial cells and hematopoietic cells in the presence of osteotropic factors such as 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], parathyroid hormone (PTH) and prostaglandin E2 (PGE2). We isolated osteoclast precursors (OCPs) from the coculture and examined their characteristics. After coculture for 7 days of mouse calvarial cells and bone marrow cells in the absence of osteotropic factors, hematopoietic cells were recovered and applied to a Sephadex G-10 column. Cells which passed through the column were collected as OCPs. When OCPs were cultured on calvarial cell layers in the presence of 1alpha,25(OH)2D3, tartrate-resistant acid phosphatase (TRAP)-positive cells first appeared within 24 h, and their number increased thereafter. OCPs also differentiated into TRAP-positive cells within 48 h on the calvarial cell layer which had been pretreated with either 1alpha,25(OH)2D3, PTH, or PGE2. Autoradiography using [125I]-labeled calcitonin showed that TRAP-positive cells formed on the calvarial cell layer expressed calcitonin receptors. Direct contact between OCPs and calvarial cells was required for the differentiation of OCPs into TRAP-positive cells. Flow cytometric analysis revealed that OCPs were positive for Mac-1, Mac-2, and Gr-1 but negative for F4/80, B220 and CD3e. Calvarial cells obtained from macrophage-colony stimulating factor (M-CSF)-deficient osteopetrotic (op/op) mice did not support OCP formation. A cell preparation disaggregated from long bones of newborn mice contained OCPs that differentiated into TRAP-positive cells on calvarial cells within 48 h, but cell preparations of freshly isolated bone marrow cells and alveolar macrophages did not. These results suggest that OCPs are specific cells which are formed only in the bone microenvironment and that OCPs recognize a signal(s) expressed by stromal cells in response to osteotropic factors and differentiate into osteoclasts.
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PMID:Isolation and characterization of osteoclast precursors that differentiate into osteoclasts on calvarial cells within a short period of time. 973 42

Human blood monocytes can differentiate into osteoclast-like cells when they are cultured in the presence of anti-FRP-1. Messenger (mRNA) expression of markers related to osteoclasts was analyzed during differentiation of osteoclasts from monocytes. As markers related to osteoclasts, we selected cathepsin-K, carbonic anhydrase (CA) II, vacuolar H(+)-ATPase (v-ATPase), vitronectin receptor (VNR), tartrate-resistant acid phosphatase (TRAP), osteopontin (OPN), galectin-3, c-src, c-fos, and c-fms. The mRNAs other than c-src mRNA were expressed in freshly isolated monocytes or monocytes incubated with control antibody or anti-FRP-1 monoclonal antibody (MAb) for 14 days. Of these mRNAs, cathepsin-K, CA II, v-ATPase, VNR, TRAP, OPN, and c-fms mRNAs were expressed at higher levels in the osteoclast-like cells than those in monocytes cultured with control antibody. On the other hand, galectin-3 mRNA was expressed at lower levels in the osteoclast-like cells, and there was no significant difference in c-fos mRNA expression between the monocytes cultured with control antibody and anti-FRP-1 MAb. c-src mRNA could not be detected in monocytes freshly isolated or incubated with control antibody. Surprisingly, expression of c-src mRNA was induced in monocytes by anti-FRP-1 MAb and was detectable as early as 3 h after anti-FRP-1 MAb treatment, indicating that c-src is selectively induced by anti-FRP-1 MAb treatment. Furthermore, the osteoclast-like cells expressed calcitonin receptor. Receptor activator of NF-kappaB (RANK) mRNA was detectable in freshly isolated monocytes or monocytes cultured with control antibody or anti-FRP-1 MAbs. Maximal expression of RANK was observed in osteoclast-like cells. On the other hand, no receptor activator of NF-KB ligand (RANKL) mRNA was detectable in any of the samples, suggesting that anti-FRP-1 mAb can induce osteoclast-like cells from blood monocytes without RANKL.
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PMID:Gene expression during osteoclast-like cell formation induced by antifusion regulatory protein-1/CD98/4F2 monoclonal antibodies (MAbs): c-src is selectively induced by anti-FRP-1 MAb. 1067 16

We have isolated osteoclast precursors (OCPs) from cocultures of mouse calvarial cells and bone marrow cells without adding any osteotropic factors. OCPs expressed Mac-1, Mac-2, and Gr-1 antigens but not osteoclast markers such as tartrate-resistant acid phosphatase (TRAP) and calcitonin receptors, and they differentiated into TRAP-positive cells within 48 h on a fixed calvarial cell layer pretreated with osteotropic factors such as 1 alpha, 25-dihydroxyvitamin D3. In the present study, we investigated the regulatory mechanisms of OCP formation from hemopoietic cells and TRAP-positive cell formation from OCPs. Calvarial osteoblasts obtained from macrophage-colony stimulating factor (M-CSF)-deficient op/op mice failed to support OCP formation or the differentiation of OCPs into TRAP-positive cells. Both OCP formation and TRAP-positive cell formation supported by osteoblasts were completely inhibited by osteoclastogenesis inhibitory factor (OCIF, also called OPG), which is a decoy receptor of osteoclast differentiation factor (ODF; also called TRANCE, RANKL, and OPGL). When bone marrow cells were cultured for 4 days with soluble ODF (sODF/sRANKL) together with M-CSF, OCPs were formed even in the absence of osteoblasts. When OCPs were treated with sODF/sRANKL and M-CSF in the absence of osteoblasts, they differentiated into TRAP-positive cells within 48 h even in the presence of hydroxyurea. Northern blotting analysis revealed that osteoblasts constitutively expressed a certain level of ODF/RANKL mRNA. These results indicated that M-CSF and sODF/sRANKL produced by osteoblasts are two essential factors for both OCP formation and TRAP-positive osteoclast formation.
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PMID:Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. 1087 96

Bone-lining tissues contain a population of resident macrophages termed osteomacs that interact with osteoblasts in vivo and control mineralization in vitro. The role of osteomacs in bone repair was investigated using a mouse tibial bone injury model that heals primarily through intramembranous ossification and progresses through all major phases of stabilized fracture repair. Immunohistochemical studies revealed that at least two macrophage populations, F4/80(+) Mac-2(-/low) TRACP(-) osteomacs and F4/80(+) Mac-2(hi) TRACP(-) inflammatory macrophages, were present within the bone injury site and persisted throughout the healing time course. In vivo depletion of osteomacs/macrophages (either using the Mafia transgenic mouse model or clodronate liposome delivery) or osteoclasts (recombinant osteoprotegerin treatment) established that osteomacs were required for deposition of collagen type 1(+) (CT1(+)) matrix and bone mineralization in the tibial injury model, as assessed by quantitative immunohistology and micro-computed tomography. Conversely, administration of the macrophage growth factor colony-stimulating factor 1 (CSF-1) increased the number of osteomacs/macrophages at the injury site significantly with a concurrent increase in new CT1(+) matrix deposition and enhanced mineralization. This study establishes osteomacs as participants in intramembranous bone healing and as targets for primary anabolic bone therapies.
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PMID:Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. 2130 7

Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche.
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PMID:Galectin-3 Cleavage Alters Bone Remodeling: Different Outcomes in Breast and Prostate Cancer Skeletal Metastasis. 2683 63