Upregulation by retinoic acid of transforming growth factor-β-stimulated heat shock protein 27 induction in osteoblasts: involvement of mitogen-activated protein kinases

Abstract

We investigated whether transforming growth factor-beta (TGF-beta) stimulates the induction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E1 cells and the mechanism underlying the induction. TGF-beta increased the level of HSP27 but had no effect on the HSP70 level. TGF-beta stimulated the accumulation of HSP27 dose-dependently, and induced an increase in the level of mRNA for HSP27. TGF-beta induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TGF-beta was significantly suppressed by PD98059, an inhibitor of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase. PD98059 and SB203580 suppressed the TGF-beta-stimulated increase in the level of mRNA for HSP27. Retinoic acid, a vitamin A (retinol) metabolite, which alone had little effect on the HSP27 level, markedly enhanced the HSP27 accumulation stimulated by TGF-beta. Retinoic acid enhanced the TGF-beta-induced increase of mRNA for HSP27. The amplification of TGF-beta-stimulated HSP27 accumulation by retinoic acid was reduced by PD98059 or SB203580. Retinoic acid failed to affect the TGF-beta-induced phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. These results strongly suggest that p44/p42 MAP kinase and p38 MAP kinase take part in the pathways of the TGF-beta-stimulated HSP27 induction in osteoblasts, and that retinoic acid upregulates the TGF-beta-stimulated HSP27 induction at a point downstream from p44/p42 MAP kinase and p38 MAP kinase.

HSP25 Affects the Proliferation and Differentiation of Rat Dental Follicle Cells

“…A recent study reported that heat stress not only induced HSP25 but also promoted ALP activity in cultured dental pulp cells (Lee et al, 2008). Similarly, in the present study, murine recombinant HSP25 directly enhanced the ALP activity of DFCs, in accordance with results from other studies that indicated that HSP25 could be induced in osteoblasts via protein kinase C (PKC), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) (Kozawa et al, 2001;Tokuda et al, 2002;Hatakeyama et al, 2002;Takai et al, 2006). Moreover, PKC gene elevation may be critical to OPG regulation in DFCs (Wise et al, 2003), and VEGF, BMP2 and BMP7 may lead DFCs to a cementoblast/osteoblast pathway through MAPK involvement (Chen et al, 2007;Kémoun et al, 2007).…”

“…The protein was also used as a useful marker for the differentiation of the odontoblasts while detecting pulpal responses to laser and cavity preparation (Suzuki et al, 2004;Kawagishi et al, 2006). The role of HSP25 in signal transduction of osteoblasts has also been studied widely (Kozawa et al, 2001;Hatakeyama et al, 2002;Tokuda et al, 2002;Takai et al, 2006). Though HSP25 was strongly suspected to be a marker protein in tooth development, limited information about its expression in DFCs is available.…”

Serum antibody titers against heat shock protein 27 are associated with the severity of coronary artery disease

“…More importantly, the high levels of serum anti-Hsp27 titers in CAD + and CAD − subjects as well as subjects with acute coronary syndrome (GhayourMobarhan et al 2008) could be attributed to the underlying inflammatory vascular disease (e.g., atherosclerosis). The expression and phosphorylation of Hsp27 appears to be influenced by inflammation, and there is evidence indicating direction of Hsp27 expression and phosphorylation by cytokines (Hastie et al 1997;Hatakeyama et al 2002;Njemini et al 2006). There are also several reports on the role of Hsp27 in regulating the inflammatory response via alterations in the expression of pro-and anti-inflammatory mediators (De et al 2000 andPark et al 2003;Sur et al 2008;Liu et al 2010).…”

Transforming Growth Factor .BETA.1 Promotes Migration of Human Periodontal Ligament Cells through Heat Shock Protein 27 Phosphorylation

“…19,21) Several lines of evidence have shown that Hsp27 directly participates in TGF-b-regulated physiological processes. 22,23) For example, invasive and metastatic potential induced by TGF-b1 correlate with Hsp27 expression in gastric cancer cells.…”