1,25 dihydroxyvitamin D3 and dexamethasone induce the cyclooxygenase 1 gene in osteoclast-supporting stromal cells

Abstract

Commitment of members of the monocyte/macrophage family to the bone resorptive phenotype, in vitro, requires contact, of these osteoclast precursors, with osteoblasts or related stromal cells. The osteoclast-inductive properties of these stromal cells are typically expressed, however, only in the presence of steroid hormones such as 1,25 dihydroxyvitamin D (1,25D3) and dexamethasone (DEX). To gain insight into the means by which steroid treated accessory cells induce osteoclast differentiation we asked, using differential RNA display (DRD), if gene expression by this stromal cell population differs from that of their untreated, non-osteoclastogenic counterpart. We identified four known genes specifically expressed by 1,25D3/DEX-treated ST2 stromal cells: 1) a family of rat organic anion transporters, 2) Na/K ATPase ss-subunit, 3) tazarotene-induced gene 2 (TIG2), and 4) prostaglandin G/H synthase I, or cyclooxygenase 1 (Cox-1). The regulation of these genes in 1,25D3/DEX-treated ST2 cells was demonstrated by Northern blot analysis of treated (osteoclast-supporting) and untreated (non-osteoclast-supporting) ST2 cells; the genes have a limited and specific tissue mRNA expression pattern. Northern blot analysis of treated and untreated ST2 cell total RNA using either a DRD-derived Cox-1 cDNA or a Cox-1 specific oligonucleotide confirmed the steroid regulation of Cox-1 mRNA. Surprisingly, there is no detectable expression by untreated or steroid exposed ST2 cells, of Cox-2, the classical regulated cyclooxygenase isoform. In contrast to 1, 25D3/DEX, serum treatment rapidly induces Cox-2 mRNA, substantiating the capacity of ST2 cells to express the gene. These data establish that steroid induction of the osteoclastogenic properties of stromal cells is attended by Cox gene expression, a phenomenon consistent with the capacity of eicosinoids to impact the resorptive process. The response of osteoclast-supporting ST2 cells to 1,25D3/DEX treatment may be one prostaglandin-mediated event which specifically involves Cox-1 regulation.

Chemokine-Like Receptor 1 Expression and Chemerin-Directed Chemotaxis Distinguish Plasmacytoid from Myeloid Dendritic Cells in Human Blood

“…It was also shown to be up-regulated in a hormone-treated, osteoclastogenic mouse bone marrow stromal cell line ST2 (35). Indeed, we found that conditioned medium from the ST2 cell line treated with 1,25-dihydroxyvitamin D 3 and dexamethasone was chemotactic for CMKLR1 transfectants (data not shown).…”

Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohnʼs disease

“…Dexamethasone in combination with 1,25 dihydroxivitamin D3 induces chemerin in osteoclast-supporting stromal cells [38] but the effects of steroids alone on chemerin expression have not been analysed in detail so far.…”

Activation of Protease-Activated Receptor-2 Leads to Inhibition of Osteoclast Differentiation

“…The fact that PAR-2 caused a suppression of expression of the supposedly constitutive PGHS-1 in 3-day bone marrow cultures was not entirely surprising, because this enzyme has previously been found to be regulated in ST2 stromal cells. (37) What is the physiological significance of our observation that PAR-2 activation results in inhibition of PTH-and 1,25(OH) 2 D 3 -induced osteoclast differentiation? The PAR-2-null mice used in this study had grossly normal skeletons, (27) and PAR-2-null mice from other groups are also described as being grossly normal, (38,39) although no detailed study of bone development and structure has yet been carried out.…”