Extracellular S100A4 negatively regulates osteoblast function by activating the NF-κB pathway
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Patients with inflammatory bone disease or cancer exhibit an increased risk of fractures and delayed bone healing. The S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. We investigated the effects of extracellular S100A4 on osteoblasts, which are cells responsible for bone formation. Treating primary calvarial osteoblasts with recombinant S100A4 resulted in matrix mineralization reductions. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed. Interestingly, S100A4 stimulated the nuclear factor-kappaB (NF-κB) signaling pathway in osteoblasts. More importantly, the ex vivo organ culture of mouse calvariae with recombinant S100A4 decreased the expression levels of osteocalcin, supporting the results of our in vitro experiments. This suggests that extracellular S100A4 is important for the regulation of bone formation by activating the NF-κB signaling pathway in osteoblasts.
Abstract
Patients with inflammatory bone disease or cancer exhibit an increased risk of fractures and delayed bone healing. The S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. We investigated the effects of extracellular S100A4 on osteoblasts, which are cells responsible for bone formation. Treating primary calvarial osteoblasts with recombinant S100A4 resulted in matrix mineralization reductions. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed. Interestingly, S100A4 stimulated the nuclear factor-kappaB (NF-κB) signaling pathway in osteoblasts. More importantly, the ex vivo organ culture of mouse calvariae with recombinant S100A4 decreased the expression levels of osteocalcin, supporting the results of our in vitro experiments. This suggests that extracellular S100A4 is important for the regulation of bone formation by activating the NF-κB signaling pathway in osteoblasts.
참고문헌 (28)
- Heizmann CW, "S100 proteins: structure, functions and pathology", Front Biosci, 7, pp.d1356~d1368 (2002)
- Roth J, "Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules", Trends Immunol, 24, pp.155~158 (2003)
- Emberley ED, "S100 proteins and their influence on pro-survival pathways in cancer", Biochem Cell Biol, 82, pp.508~515 (2004)
- Foell D, "Expression of the pro-inflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis", Rheumatology (Oxford), 42, pp.1383~1389 (2003)
- Grevers LC, "S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll-like receptor 4: implications for bone destruction in murine antigen-induced arthritis", Arthritis Rheum, 63, pp.1365~1375 (2011)
- Klingelhofer J, "Upregulation of metastasis-promoting S100A4 (Mts-1) in rheumatoid arthritis: putative involvement in the pathogenesis of rheumatoid arthritis", Arthritis Rheum, 56, pp.779~789 (2007)
- Yammani RR, "Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products", Arthritis Rheum, 54, pp.2901~2911 (2006)
- Sherbet GV, "Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy", Cancer Lett, 280, pp.15~30 (2009)
- Boye K, "S100A4 and metastasis: a small actor playing many roles", Am J Pathol, 176, pp.528~535 (2010)
- Chang J, "Inhibition of osteoblastic bone formation by nuclear factor-kappaB", Nat Med, 15, pp.682~689 (2009)
- Chang J, "NF-kappaB inhibits osteogenic differentiation of mesenchymal stem cells by promoting beta-catenin degradation", Proc Natl Acad Sci U S A, 110, pp.9469~9474 (2013)
- Yamazaki M, "Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB", J Biol Chem, 284, pp.35987~35995 (2009)
- Hofmann MA, "RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100", calgranulin polypeptides, 1999, pp.97, 889~901
- Ogawa N, "The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs", Horm Metab Res, 39, pp.871~875 (2007)
- 최식원, "Suppression of Akt-HIF-1α signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis", BMB Reports, 49(9), pp.508~513 (2016), 생화학분자생물학회
- 박경록, "Regulator of calcineurin 1-4과 파골세포 분화의 관련성", 생명과학회지, 25(2), pp.223~230 (2015), 한국생명과학회
- Liangbo Lin, "Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1", 2 mesenchymal stem cells, 2016, pp.49(3), 179~184[DOI]
- Gilbert L, "Inhibition of osteoblast differentiation by tumor necrosis factor-alpha", Endocrinology, 141, pp.3956~3964 (2000)
- Gilbert L, "Expression of the osteoblast differentiation factor RUNX2(Cbfa1", AML3, J Biol Chem, pp.2002, 277[DOI]
- Kaneki H, "Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts", J Biol Chem, 281, pp.4326~4333 (2006)
- Jang WG, "Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory Actions of Tumor Necrosis Factor alpha in Osteoblast Differentiation by Stimulating Smad1 Degradation", J Biol Chem, 290, pp.13556~13566 (2015)
- Lee ZH, "Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts", Biochem Biophys Res Commun, 305, pp.211~214 (2003)
- Erlandsson MC, "Expression of metastasin S100A4 is essential for bone resorption and regulates osteoclast function", Biochim Biophys Acta, 1833, pp.2653~2663 (2013)
- Mah SJ, "Induction of S100A4 in periodontal ligament cells enhances osteoclast formation", Arch Oral Biol, 60, pp.1215~1221 (2015)
- Cerezo LA, "The metastasis-associated protein S100A4 promotes the inflammatory response of mononuclear cells via the TLR4 signalling pathway in rheumatoid arthritis", Rheumatology (Oxford), 53, pp.1520~1526 (2014)
- Herwig N, "Interaction of extracellular S100A4 with RAGE prompts prometastatic activation of A375 melanoma cells", J Cell Mol Med, 20, pp.825~835 (2016)
- Medapati MR, "RAGE Mediates the Pro-Migratory Response of Extracellular S100A4 in Human Thyroid Cancer Cells", Thyroid, 25, pp.514~527 (2015)
- Siddique HR, "The S100A4 Oncoprotein Promotes Prostate Tumorigenesis in a Transgenic Mouse Model: Regulating NFkappaB through the RAGE Receptor", Genes Cancer, 4, pp.224~234 (2013)