Signal transduction and transcriptional regulation during mesenchymal cell differentiation

Nishimura, Riko; Hata, Kenji; Ikeda, Fumiyo; Ichida, Fumitaka; Shimoyama, Atsuko; Matsubara, Takuma; Wada, Masahiro; Amano, Katsuhiko; Yoneda, Toshiyuki

doi:10.1007/s00774-007-0824-2

Cited by 92 publications

(73 citation statements)

References 107 publications

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“…A complex molecular network of signaling pathways and regulatory factors governs the osteogenesis of multipotent MSCs [17,18,27], being reliant on the activation and regulation of a number of key molecular targets including RUNX2, ALP, SPP1, and IBSP [28]. Although there have been significant advances in our understanding of the molecular mechanisms involved in controlling osteogenic differentiation, the influence of serine proteases on such processes remains relatively obscure.…”

Section: Discussionmentioning

confidence: 99%

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

et al. 2012

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Mammalian high-temperature requirement serine protease A1 (HTRA1) is a secreted member of the trypsin family of serine proteases which can degrade a variety of bone matrix proteins and as such has been implicated in musculoskeletal development. In this study, we have investigated the role of HTRA1 in mesenchymal stem cell (MSC) osteogenesis and suggest a potential mechanism through which it controls matrix mineralization by differentiating boneforming cells. Osteogenic induction resulted in a significant elevation in the expression and secretion of HTRA1 in MSCs isolated from human bone marrow-derived MSCs (hBMSCs), mouse adipose-derived stromal cells (mASCs), and mouse embryonic stem cells. Recombinant HTRA1 enhanced the osteogenesis of hBMSCs as evidenced by significant changes in several osteogenic markers including integrin-binding sialoprotein (IBSP), bone morphogenetic protein 5 (BMP5), and sclerostin, and promoted matrix mineralization in differentiating boneforming osteoblasts. These stimulatory effects were not observed with proteolytically inactive HTRA1 and were abolished by small interfering RNA against HTRA1. Moreover, loss of HTRA1 function resulted in enhanced adipogenesis of hBMSCs. HTRA1 Immunofluorescence studies showed colocalization of HTRA1 with IBSP protein in osteogenic mASC spheroid cultures and was confirmed as being a newly identified HTRA1 substrate in cell cultures and in proteolytic enzyme assays. A role for HTRA1 in bone regeneration in vivo was also alluded to in bone fracture repair studies where HTRA1 was found localized predominantly to areas of new bone formation in association with IBSP. These data therefore implicate HTRA1 as having a central role in osteogenesis through modification of proteins within the extracellular matrix. STEM CELLS

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Section: Discussionmentioning

confidence: 99%

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

et al. 2012

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“…Dessa maneira, as existências de fatores regulatórios formam microambientes indutivos (TRENTIN, 1978;TESTA;DEXTER, 1990) que controlam a hematopoese pela produção e secreção local de citocinas pelas células do estroma, co-localização de citocinas para a CTH nos locais de contato célula -célula e, ou célula -MEC ou ainda, por estímulo direto pelo contato celular (RIOS; WILLIAMS, 1990;METCALF, 1992;OPAS, 1994 (NISHIMURA et al, 2008).…”

Section: Hematopoese -Desnutrição E Estroma Medularunclassified

“…Osso é um tecido conectivo especializado que dá suporte estrutural para o músculo esquelético, proteção física aos órgãos como cérebro e coração, reserva minerais como cálcio e fosfato e fonte continua de CTHs para a regeneração das células sanguíneas e do sistema imune (NISHIMURA et al, 2008 …”

Section: Hematopoese -Desnutrição E Estroma Medularunclassified

“…RUNX2 é o fator de transcrição responsável pela ativação do gene da osteocalcina, regulando a transcrição da osteocalcina, osteopondina e proteína sialo-osso (KOMORI, 2003;NISHIMURA et al, 2008). É expresso em duas isoformas que diferem na porção N-terminal (KOMORI; KISHIMOTO, 1998).…”

Section: Runx2unclassified

“…É também expressado em condrócitos hipertróficos e camundongos deficientes de RUNX2 mostram severos prejuízos na condrogênese nesses estágios (NISHIMURA et al, 2008;KOMORI, 2010). Requer Cbfß (fator ligante do núcleo beta), fator co-transcripicional que forma heterodímero com RUNX2 (KOMORI, 2003), para associar firmemente ao DNA e por isso …”

Section: Runx2unclassified

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Signal transduction and transcriptional regulation during mesenchymal cell differentiation

Cited by 92 publications

References 107 publications

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

Influência da desnutrição proteica sobre a expressão de fatores de transcrição envolvidos no processo de diferenciação da célula tronco mesenquimal medular

Regulation and Differentiation Potential of Dental Mesenchymal Stem Cells

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