Proteomic identification of differently expressed proteins responsible for osteoblast differentiation from human mesenchymal stem cells

Zhang, Aixia; Yu, Weihua; Ma, Baofeng; Yu, Xinbing; Mao, Frank Fuxiang; Liu, Wei; Zhang, Jiaqing; Zhang, Xiuming; Shu-nong, LI; Li, Mingtao; Lahn, Bruce T.; Xiang, Andy Peng

doi:10.1007/s11010-007-9497-3

Cited by 60 publications

(59 citation statements)

References 72 publications

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“…Cells remained viable and constrained to the patterns for one week in culture, though at longer times the nonadhesive regions were degraded and cells escaped the pattern and proliferated. To determine if shape alone can induce differentiation within this timeframe, MSCs on the patterned surfaces were exposed to growth media for one week and stained with lineage specific markers (adipocyte/OilRedO (32) and osteoblast/ alkaline phosphatase (33)). Under these conditions more than 95% of the MSCs did not show lineage specific staining.…”

Section: Resultsmentioning

confidence: 99%

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Geometric cues for directing the differentiation of mesenchymal stem cells

Kilian

Bugarija

Lahn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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1,634

1,559

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Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature-and with each occupying the same area-display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated winglesstype (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates. were initially isolated from bone marrow and noted for their ability to differentiate into bone cells (osteoblasts), cartilage cells (chondrocytes), and fat cells (adipocytes) (1, 2). As an autologous source of stem cells, MSCs are under considerable scrutiny for regenerative therapies (3). A combination of physical, chemical, and biological cues present in the stem cell microenvironment have been implicated as directors of stem cell fate in vivo (4). This concept of a stem cell "niche" has motivated empirical studies to identify optimal combinations of extracellular matrix, culture conditions, and temporally administered growth factors to direct stem cell fate in the laboratory (5-7). However, the physical forces and geometry of the MSC microenvironment remain poorly defined and have begun to emerge as critical parameters for regulating cell fate (8, 9).Physical cues, which were postulated as important factors in tissue development over a century ago (10), have also been recognized as important factors in controlling cell function. Research along these lines has been driven in the past decades with the maturation of microengineering techniques (11-13). Ingber, Whitesides, and colleagues demonstrated the use of substrates that were geometrically patterned to control the microenvironment of individual cells and in turn the decision of cells to initiate apoptosis (14). Patterned substrates have also been used to study cytoskeletal dynamics (15-18) and motility (19-22) with singlecell resolution. Chen and coworkers recently demonstrated the important role that cell shape and size can play ...

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Section: Resultsmentioning

confidence: 99%

“…Human MSCs were a gift from Dr. Andy Xiang Peng at Sun YatSen University, and derived as described (33). Cells were cultured in DMEMlow glucose supplemented with 10% FBS, 1% penicillin/streptomycin, passaged at 70-80% confluency and seeded at ∼5; 000 cells∕cm 2 .…”

Section: Methodsmentioning

confidence: 99%

Geometric cues for directing the differentiation of mesenchymal stem cells

Kilian

Bugarija

Lahn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

1,634

1,559

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“…hMSC proteomics during bone differentiation has been characterized earlier in many studies, including our own previous work [35,[44][45][46]. Here, the aim was to specifically focus on precise characterization of the exocytosed proteins that are peripherally attached to cell surface as well as glycoproteoglycansins and to compare the plasma membrane attached to BMMSC and UCBMSC secretomes, which has not been previously done.…”

mentioning

confidence: 99%

Mitochondrial Function and Energy Metabolism in Umbilical Cord Blood- and Bone Marrow-Derived Mesenchymal Stem Cells

Pietilä

Palomäki

Lehtonen

et al. 2012

Stem Cells and Development

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Human mesenchymal stem cells (hMSCs) are an attractive choice for a variety of cellular therapies. hMSCs can be isolated from many different tissues and possess unique mitochondrial properties that can be used to determine their differentiation potential. Mitochondrial properties may possibly be used as a quality measure of hMSC-based products. Accordingly, the present work focuses on the mitochondrial function of hMSCs from umbilical cord blood (UCBMSC) cells and bone marrow cells from donors younger than 18 years of age (BMMSC <18) and those more than 50 years of age (BMMSC >50). Changes of ultrastructure and energy metabolism during osteogenic differentiation in all hMSC types were studied in detail. Results show that despite similar surface antigen characteristics, the UCBMSCs had smaller cell surface area and possessed more abundant rough endoplasmic reticulum than BMMSC >50. BMMSC <18 were morphologically more UCBMSC-like. UCBMSC showed dramatically higher mitochondrial-to-cytoplasm area ratio and elevated superoxide and manganese superoxide dismutase (MnSOD) levels as compared with BMMSC >50 and BMMSC <18. All hMSCs types showed changes indicative of mitochondrial activation after 2 weeks of osteogenic differentiation, and the increase in mitochondrial-to-cytoplasm area ratio appears to be one of the first steps in the differentiation process. However, BMMSC >50 showed a lower level of mitochondrial maturation and differentiation capacity. UCBMSCs and BMMSCs also showed a different pattern of exocytosed proteins and glycoproteoglycansins. These results indicate that hMSCs with similar cell surface antigen expression have different mitochondrial and functional properties, suggesting different maturation levels and other significant biological variations of the hMSCs. Therefore, it appears that mitochondrial analysis presents useful characterization criteria for hMSCs intended for clinical use.

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“…It controls the non-oxidative part of the pentose phosphate pathway [14]. Tkt was among the 52 upregulated proteins responsible for the differentiation of mesenchymal stem cells into osteoblasts [15]. Coronin 1b (CRN1b) is an actin binding protein, which has been involved in a variety of cellular processes that include fibroblast migration [16].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of mineralising osteoblasts identifies novel genes related to bone matrix mineralisation

Saad

Hofstaetter

2010

International Orthopaedics (SICOT)

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Bone matrix mineralisation plays a critical role in the determination of the overall biomechanical competence of bone. However, the molecular mechanisms of bone matrix mineralisation have not been fully elucidated. We used a proteomic approach to identify proteins and genes that may play a role in osteoblast matrix mineralisation. Proteomic differential display revealed a protein band that appeared only in mineralising mouse 7F2 osteoblasts. In-gel protein digestion and mass spectrometry proteomic analysis of this protein band identified 16 proteins. Furthermore, their corresponding transcripts were upregulated. This identification of proteins that may be associated with bone matrix mineralisation presents important new information toward a better understanding of the precise mechanisms of this process.

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Proteomic identification of differently expressed proteins responsible for osteoblast differentiation from human mesenchymal stem cells

Cited by 60 publications

References 72 publications

Geometric cues for directing the differentiation of mesenchymal stem cells

Geometric cues for directing the differentiation of mesenchymal stem cells

Mitochondrial Function and Energy Metabolism in Umbilical Cord Blood- and Bone Marrow-Derived Mesenchymal Stem Cells

Proteomic analysis of mineralising osteoblasts identifies novel genes related to bone matrix mineralisation

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