Carbonic anhydrase II is induced in HL‐60 cells by 1,25‐dihydroxyvitamin D<sub>3</sub>: A model for osteoclast gene regulation

Shapiro, Linda H.; Venta, Patrick J.; Yu, Y.-S. L.; Tashian, Richard E.

doi:10.1016/0014-5793(89)80647-7

Cited by 33 publications

(13 citation statements)

References 28 publications

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“…First, the isolation procedures and culture conditions that we have used are known to markedly enrich for cells in this lineage (5,13,31,35). Second, 1,25(OH)2D3 also induced the expression of CAII in a homogeneous marrow-derived avian myelomonocytic cell line (BM2), a result consistent with the recent report of Shapiro et al (30) (10-8 M) did not induce the expression of detectable levels of CAI. This would suggest that these myelomonocytic cells must pass through an LPS/PMA sensitive step in order to acquire CAII responsiveness to vitamin D3.…”

Section: Discussionsupporting

confidence: 80%

“…We find that the levels of expression of CAII mRNA and protein are markedly increased by 1,25(OH)2D3 during the in vitro differentiation of normal bone marrow precursors. This was also observed in a transformed myelomonocytic cell line (BM2), thereby confirming a recent report in the transformed human monocytic cell line HL60 (30). These results suggest that 1,25(OH)2D3 acts directly on myelomonocytic precursor cells to induce expression of CAII, a protein that is present at high levels in the fully differentiated osteoclast.…”

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confidence: 76%

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1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

Billecocq

Emanuel

Levenson

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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la,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of the steroid hormone vitamin D, is a potent regulator of macrophage and osteoclast differentiation. The mature osteoclast, unlike the circulating monocyte or the tissue macrophage, expresses high levels of carbonic anhydrase H (CAH). This enzyme generates protons and bicarbonate from water and carbon dioxide and is involved in bone resorption and acid-base regulation. To test whether 1,25(OH)2D3 could induce the differentiation of myelomonocytic precursors toward osteoclasts rather than macrophages, we analyzed its effects on the expression of CAll in bone marrow cultures containing precursors common to both cell types. The expression of CAU was markedly increased by 1,25(OH)2D3 in a doseand time-dependent manner. In bone marrow, this increase occurred at the mRNA and protein levels and was detectable as early as 24 hr after stimulation. 1,25(OH)2D3 was also found to induce CAH expression in a transformed myelomonocytic avian cell line. These results suggest that 1,25(OH)2D3 regulates the level at which myelomonocytic precursors express CAU, an enzyme that is involved in the function of the mature osteoclast. la,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is the active metabolite of the steroid hormone vitamin D (1). This metabolite regulates the differentiation of osteoclasts and macrophages, two cell types that are thought to be derived from a common myelomonocytic precursor (2-6). 1,25(OH)2D3 induces an increase in bone resorption in vivo (1, 7) and in organ cultures (8, 9) but has no effect on the resorptive activity of isolated osteoclasts (10, 11). The increase in bone resorption is believed to be mediated primarily by means of an effect upon the proliferation and/or differentiation of osteoclast precursors within the hematopoietic bone marrow (12-15), leading to an increase in the number of mature osteoclasts (7,9 (13,14,19,20) and increases the proportion ofthe cells that can resorb bone (14).Taken together, these results suggest that this steroid hormone may specifically induce the differentiation of myelomonocytic precursors toward the macrophage and/or osteoclast lineage.One of the genes that is expressed at high levels in the osteoclast (21-23), but not in peripheral monocytes or mature macrophages (24), is the gene encoding carbonic anhydrase II (CAII). CAII is an enzyme that reversibly generates bicarbonate and protons from carbon dioxide and water (25). This enzyme plays an essential role in acid-secreting cells such as the kidney tubule intercalated cell (26), the gastric mucosa oxyntic cell (27), and the osteoclast (21). In humans, defective CAII is associated with cerebral calcification, tubular acidosis, and osteopetrosis (28), providing genetic evidence for CAII involvement in bone resorption. An analogue of the human disease has been produced by chemical mutagenesis in the mouse, where CAII deficiency is associated with renal tubular acidosis and vascular calcification but no major bone defects (29).We have investigated wheth...

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Section: Discussionsupporting

confidence: 80%

supporting

confidence: 76%

1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

Billecocq

Emanuel

Levenson

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The importance of CAII in the function of osteoclasts is best demonstrated by the fact that mutation ofthe CAII-encoding gene is associated with osteopetrosis, renal tubular acidosis, and cerebral calcification (4). Furthermore, inhibition of CAII in vitro induces a decrease in bone resorption (5), and CAII activity and levels of expression can be regulated by calciotropic and thyroid hormones (6)(7)(8)(9). This regulation includes la,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of the steroid hormone vitamin D, which regulates CAII mRNA and protein levels in human and avian mononuclear phagocytes (7,8).…”

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confidence: 99%

“…Furthermore, inhibition of CAII in vitro induces a decrease in bone resorption (5), and CAII activity and levels of expression can be regulated by calciotropic and thyroid hormones (6)(7)(8)(9). This regulation includes la,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of the steroid hormone vitamin D, which regulates CAII mRNA and protein levels in human and avian mononuclear phagocytes (7,8). The action of steroid hormones involves their high-affinity binding to specific receptors in nuclei, and the regulation of specific gene transcription is mediated by binding of the hormone-receptor complex to steroid-responsive elements present in the promoter regions of the affected genes (10).…”

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1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes.

Lomri

Baron

1992

Proc. Natl. Acad. Sci. U.S.A.

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Carbonic anhydrase II (CAII) is highly expressed in the osteoclast, where it is involved in the process of extracellular acidification required for bone resorption. We have previously shown that la,25-dihydroxyvitamin D3 [1,25(OH) (1), and the osteoclast in bone (2, 3). In all these cells, the role of CAII is to generate H+ for acid extrusion by the ATP-driven proton pumps, and HCO-is usually extruded via bicarbonate/chloride exchangers. The importance of CAII in the function of osteoclasts is best demonstrated by the fact that mutation ofthe CAII-encoding gene is associated with osteopetrosis, renal tubular acidosis, and cerebral calcification (4). Furthermore, inhibition of CAII in vitro induces a decrease in bone resorption (5), and CAII activity and levels of expression can be regulated by calciotropic and thyroid hormones (6-9). This regulation includes la,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of the steroid hormone vitamin D, which regulates CAII mRNA and protein levels in human and avian mononuclear phagocytes (7,8). The action of steroid hormones involves their high-affinity binding to specific receptors in nuclei, and the regulation of specific gene transcription is mediated by binding of the hormone-receptor complex to steroid-responsive elements present in the promoter regions of the affected genes (10). Although analysis of the CAII gene suggested the possibility that the promoter region contained vitamin D-responsive elements (VDRE) (8,11,12), no change in CAII mRNA levels were observed before 24 hr in the human promonocytic cell line HL-60 (7). The present study was, therefore, done to determine whether 1,25(OH)2D3 increases CAII mRNA by acting at the transcriptional and/or posttranscriptional levels and whether this increase required the transcription and translation of other gene products.Using a transformed myelomonocytic avian cell line (BM2), we found that the regulation of CAII levels by 1,25(OH)2D3 in mononuclear phagocytes occurs mostly via an increase in gene transcription. This effect is independent of de novo protein synthesis, thereby suggesting that the effect does not require the synthesis of other gene products. MATERIALS AND METHODS 4688The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…These cells express some characteristic markers such as tartrate-resistant acid phosphatase, vitronectin receptor, calcitonin receptor, and CAII. CAII, expressed at high levels in osteoclasts (41,42), plays an important role in the extracellular acidification required for bone resorption and therefore bone remodeling. In particular, CAII deficiency is one of the factors responsible for the osteopetrosis characterized in humans by a renal tubular acidosis and a cerebral calcification (43).…”

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Identification of a Vitamin D Response Element in the Proximal Promoter of the Chicken Carbonic Anhydrase II Gene

Quélo

Machuca

Jurdic

1998

Journal of Biological Chemistry

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The carbonic anhydrase II gene, whose transcription is enhanced by 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), encodes an important enzyme in bone-resorbing cells derived from the fusion of monocytic progenitors. We analyzed the 1,25-(OH) 2 D 3 -mediated activation of the avian gene by transient transfection assays with promoter/reporter constructs into HD11 chicken macrophages and by DNA mobility shift assays. Deletion and mobility shift analyses indicated that the ؊62/؊29 region confers 1,25-(OH) 2 D 3 responsiveness and forms DNA-protein complexes. The addition of an anti-vitamin D receptor (VDR) antibody inhibited binding to this sequence, whereas anti-retinoid X receptor (RXR) antibody generated a lower mobility complex. Therefore, we concluded that this element binds a VDR⅐RXR heterodimer, but the addition of extra 1,25-(OH) 2 D 3 had no effect on the formation of this complex. Moreover, the use of nuclear extracts from 1,25-(OH) 2 D 3 -treated macrophages led to the formation of an additional high mobility complex also composed of VDR⅐RXR heterodimer. Mutations provided evidence that the 1,25-(OH) 2 D 3 -mediated activation of the carbonic anhydrase II gene is mediated by VDR⅐RXR heterodimers bound to a DR3-type vitamin D response element with sequence AGGGCAtggAGTTCG. This vitamin D response element is also functional in the ROS 17/2.8 osteoblasts.Recent work points to the complexity of the molecular mechanisms involved in the vitamin D 3 signaling pathway. It has been known for some time that in addition to the binding of the vitamin D receptor (VDR) 1 to certain vitamin D response elements (VDREs) as homodimer (3-7), the in vitro binding affinity of the VDR is enhanced by dimerization with accessory factors such as RXRs (8 -11). The response elements for these receptors differ from one another by the number of base pairs (bp) spacing the hexameric repeats according to the so-called 1 to 5 rule (1, 2). Following the 1 to 5 rule, optimal VDREs for VDR⅐RXR heterodimers should be direct repeats of two hexameric core binding sites spaced by three nucleotides (DR3) (1, 3). The high specificity of these DR3-type VDREs was confirmed by identification of some natural and synthetic VDREs (10). The mouse osteopontin VDRE has been shown to bind VDR homodimers with low affinity (3, 6, 12, 13) but VDR⅐RXR heterodimers with high affinity (3, 9, 14, 15). DR3-type elements have also been found in numerous promoters such as the rat osteocalcin gene (16,17), the rat calbindin D-9k (18), the avian integrin ␤3 subunit gene (19), the rat 24-hydroxylase gene (20 -22), the avian carbonic anhydrase II (CAII) gene (23), and mouse p21 (24). However, the binding sites of the VDREs characterized so far vary considerably in their sequences, preventing definition of a real VDRE consensus sequence (7,(25)(26)(27).The differentiating effects of 1,25-(OH) 2 D 3 have been studied extensively in a large number of in vitro systems using cultures of leukemia cells (28, 29), keratinocytes (30 -32), or bone cells (33-35). Despite this at...

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Carbonic anhydrase II is induced in HL‐60 cells by 1,25‐dihydroxyvitamin D₃: A model for osteoclast gene regulation

Cited by 33 publications

References 28 publications

1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes.

Identification of a Vitamin D Response Element in the Proximal Promoter of the Chicken Carbonic Anhydrase II Gene

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Carbonic anhydrase II is induced in HL‐60 cells by 1,25‐dihydroxyvitamin D3: A model for osteoclast gene regulation

Cited by 33 publications

References 28 publications

1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells.

1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes.

Identification of a Vitamin D Response Element in the Proximal Promoter of the Chicken Carbonic Anhydrase II Gene

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Carbonic anhydrase II is induced in HL‐60 cells by 1,25‐dihydroxyvitamin D₃: A model for osteoclast gene regulation