Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells through an ERK-dependent pathway. Mol Biol Cell

Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596, USA.
Molecular Biology of the Cell (Impact Factor: 4.55). 03/2005; 16(2):881-90. DOI: 10.1091/mbc.E04-08-0695
Source: PubMed

ABSTRACT The laminin family of proteins is critical for managing a variety of cellular activities including migration, adhesion, and differentiation. In bone, the roles of laminins in controlling osteogenic differentiation of human mesenchymal stem cells (hMSC) are unknown. We report here that laminin-5 is found in bone and expressed by hMSC. hMSC isolated from bone synthesize laminin-5 and adhere to exogenous laminin-5 through alpha3beta1 integrin. Adhesion to laminin-5 activates extracellular signal-related kinase (ERK) within 30 min and leads to phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 within 8 d. Cells plated on laminin-5 for 16 d express increased levels of osteogenic marker genes, and those plated for 21 d deposit a mineralized matrix, indicative of osteogenic differentiation. Addition of the ERK inhibitor PD98059 mitigates these effects. We conclude that contact with laminin-5 is sufficient to activate ERK and to stimulate osteogenic differentiation in hMSC.

Download full-text


Available from: Adele L Boskey, Aug 17, 2015
  • Source
    • "In a follow-up study, Biggs et al. investigated the effect nanotopographies have on the ERK/MAPK signalling pathway for STRO-1+ human MSCs [37]. The signalling cascade, extracellular signal-regulated kinase (ERK), is a known member of the MAPK pathway, shown to play a significant role in MSC differentiation [38] [39] [40]. Intricate signalling pathways, such as the ERK/MAPK pathway, play a vital role in the cellular differentiation of MSCs through translating tensions applied at the tissue level to cellular functions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs), play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controlling the osteogenic differentiation of MSCs through biomaterials, nanotopographies, and modified surfaces for use in implant procedures.
    Stem cell International 05/2013; 2013:361637. DOI:10.1155/2013/361637 · 2.81 Impact Factor
  • Source
    • "culturing them on laminin-5, which ligates integrin α 3 β 1 , activates extracellular signalregulated kinase (ERK), and leads to phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 (Klees et al. 2005). These studies demonstrate the integral role of the adhesive microenvironment in activating canonical cell signaling pathways. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stem cells reside in adult and embryonic tissues in a broad spectrum of developmental stages and lineages, and they are thus naturally exposed to diverse microenvironments or niches that modulate their hallmark behaviors of self-renewal and differentiation into one or more mature lineages. Within each such microenvironment, stem cells sense and process multiple biochemical and biophysical cues, which can exert redundant, competing, or orthogonal influences to collectively regulate cell fate and function. The proper presentation of these myriad regulatory signals is required for tissue development and homeostasis, and their improper appearance can potentially lead to disease. Whereas these complex regulatory cues can be challenging to dissect using traditional cell culture paradigms, recently developed engineered material systems offer advantages for investigating biochemical and biophysical cues, both static and dynamic, in a controlled, modular, and quantitative fashion. Advances in the development and use of such systems have helped elucidate novel regulatory mechanisms controlling stem cell behavior, particularly the importance of solid-phase mechanical and immobilized biochemical microenvironmental signals, with implications for basic stem cell biology, disease, and therapeutics.
    Annual Review of Cell and Developmental Biology 11/2010; 26(1):533-56. DOI:10.1146/annurev-cellbio-100109-104042 · 20.24 Impact Factor
  • Source
    • "For example, studies have shown that purified and cell-derived ECM proteins are important in the differentiation of ESCs to columnar and squamous epithelia [15], trophectoderm [16], pancreatic beta cells [17], and skin [18]. Although the effect of ECM on the differentiation of ESCs to bone has not yet been investigated, several previous studies have documented the effect of ECM proteins such as collagen type I, vitronectin and laminin-5 on the differentiation of marrow stromal cells (MSCs) [19] [20] [21] [22] [23], and demonstrated that such matrix-induced differentiation is partially dependent on signalling via the integrin family of cell-surface receptors [20] [24]. In another study, an ECM derived from MSCs grown in osteogenic supplements increased bone formation significantly when MSCs were re-cultured on this matrix [25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate into mineralising cells in vitro. The use of pluripotent cells in engineered bone substitutes will benefit from the development of bioactive scaffolds which encourage cell differentiation and tissue development. Extracellular matrix (ECM) may be a suitable candidate for use in such scaffolds since it plays an active role in cellular differentiation. Here, we test the hypothesis that tissue-specific ECM influences the differentiation of murine ESCs. We induced murine ESCs to differentiate by embryoid body formation, followed by dissociation and culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1) or non-osteogenic cell (A549) cultures, or on defined collagen type I matrix. We assessed osteogenic differentiation by formation of mineralised tissue and osteogenic gene expression, and found it to be significantly greater on MC3T3-E1 matrices than on any other matrix. The osteogenic effect of MC3T3-E1 matrix was reduced by heat treatment and abolished by trypsin, suggesting a bioactive proteinaceous component. These results demonstrate that decellularised bone-specific ECM promotes the osteogenic differentiation of ESCs. Our results are of fundamental interest and may help in tailoring scaffolds for tissue engineering applications which both incorporate tissue-specific ECM signals and stimulate stem-cell differentiation.
    Biomaterials 02/2010; 31(12):3244-52. DOI:10.1016/j.biomaterials.2010.01.039 · 8.31 Impact Factor
Show more