﻿%0 Journal Article
%A Uth, K.
%A Trifonov, D.
%D 2014
%T Stem cell application for osteoarthritis in the knee joint: A minireview
%J World J Stem Cells
%V 6
%N 5
%P 629-36
%8 Nov 26
%! Stem cell application for osteoarthritis in the knee joint: A minireview
%Z World Journal of Stem Cells
%@ 1948-0210 (Print)
1948-0210 (Electronic)
%R 10.4252/wjsc.v6.i5.629
%2 PMC4178263
%X Knee osteoarthritis is a chronic, indolent disease that will affect an ever increasing number of patients, especially the elderly and the obese. It is characterized by degeneration of the cartilage substance inside the knee which leads to pain, stiffness and tenderness. By some estimations in 2030, only in the United States, this medical condition will burden 67 million people. While conventional treatments like physiotherapy or drugs offer temporary relief of clinical symptoms, restoration of normal cartilage function has been difficult to achieve. Moreover, in severe cases of knee osteoarthritis total knee replacement may be required. Total knee replacements come together with high effort and costs and are not always successful. The aim of this review is to outline the latest advances in stem cell therapy for knee osteoarthritis as well as highlight some of the advantages of stem cell therapy over traditional approaches aimed at restoration of cartilage function in the knee. In addition to the latest advances in the field, challenges associated with stem cell therapy regarding knee cartilage regeneration and chondrogenesis in vitro and in vivo are also outlined and analyzed. Furthermore, based on their critical assessment of the present academic literature the authors of this review share their vision about the future of stem cell applications in the treatment of knee osteoarthritis.
%Z Uth, Kristin
Trifonov, Dimitar
World J Stem Cells. 2014 Nov 26;6(5):629-36. Epub 2014 Nov 26 doi:10.4252/wjsc.v6.i5.629.
%+ Kristin Uth, University of Oxford, Old Road Campus Research Building, Old Road Campus, Oxford OX3 7DQ, United Kingdom
Dimitar Trifonov, BioDiscovery, Dundee Science Press, Scotland DD6 8NR, United Kingdom
%G eng



%0 Journal Article
%A James, A. W.
%D 2013
%T Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation
%J Scientifica (Cairo)
%V 2013
%P 684736
%! Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation
%Z Scientifica
%@ 2090-908X (Print)
2090-908X (Linking)
%R 10.1155/2013/684736
%2 3874981
%M 24416618
%X Mesenchymal stem cells (MSC) are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor- gamma (PPAR gamma ) and Runt-related transcription factor 2 (Runx2). These two transcription factors, PPAR gamma and Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These include beta -catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP) signaling and insulin growth factor (IGF) signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.
%Z James, Aaron W
ENG
REVIEW
2014/01/15 06:00
Scientifica (Cairo). 2013;2013:684736. Epub 2013 Dec 12.
%U http://www.ncbi.nlm.nih.gov/pubmed/24416618
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874981/pdf/SCIENTIFICA2013-684736.pdf
%> internal-pdf://James-2013-Review of Signaling-1314265856/James-2013-Review of Signaling.pdf
%+ Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS A3-251, Los Angeles, CA 90077, USA.



%0 Journal Article
%A Higuchi, A.
%A Ling, Q. D.
%A Chang, Y.
%A Hsu, S. T.
%A Umezawa, A.
%D 2013
%T Physical cues of biomaterials guide stem cell differentiation fate
%J Chem Rev
%V 113
%N 5
%P 3297-328
%8 May 8
%! Physical cues of biomaterials guide stem cell differentiation fate
%Z Chemical reviews
%@ 1520-6890 (Electronic)
0009-2665 (Linking)
%R 10.1021/cr300426x
%M 23391258
%K Animals
Biocompatible Materials/*chemistry/metabolism
*Cell Differentiation
Humans
Stem Cells/*cytology/metabolism
Tissue Engineering/*methods
Tissue Scaffolds/*chemistry
%Z Higuchi, Akon
Ling, Qing-Dong
Chang, Yung
Hsu, Shih-Tien
Umezawa, Akihiro
eng
Research Support, Non-U.S. Gov't
Review
2013/02/09 06:00
Chem Rev. 2013 May 8;113(5):3297-328. doi: 10.1021/cr300426x. Epub 2013 Feb 7.
%U http://www.ncbi.nlm.nih.gov/pubmed/23391258
%+ Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan 32001, Taiwan. higuchi@ncu.edu.tw



%0 Journal Article
%A Thorfve, A.
%A Dehne, T.
%A Lindahl, A.
%A Brittberg, M.
%A Pruss, A.
%A Ringe, J.
%A Sittinger, M.
%A Karlsson, C.
%D 2012
%T Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage
%J Cartilage
%V 3
%N 1
%P 43-57
%8 Wnt在OA中的不同表达
%! Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage
%R 10.1177/1947603511414178
%X Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage.
%U http://car.sagepub.com/content/3/1/43.abstract
http://car.sagepub.com/content/3/1/43.full.pdf
%> internal-pdf://Thorfve-2012-Characteristic Marke-3344581888/Thorfve-2012-Characteristic Marke.pdf



%0 Journal Article
%A Gupta, P. K.
%A Das, A. K.
%A Chullikana, A.
%A Majumdar, A. S.
%D 2012
%T Mesenchymal stem cells for cartilage repair in osteoarthritis
%J Stem Cell Res Ther
%V 3
%N 4
%P 25
%! Mesenchymal stem cells for cartilage repair in osteoarthritis
%Z Stem Cell Research & Therapy
%@ 1757-6512 (Electronic)
%M 22776206
%X Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.
%Z Gupta, Pawan K
Das, Anjan K
Chullikana, Anoop
Majumdar, Anish S
Stem Cell Res Ther. 2012;3(4):25. doi:10.1186/scrt116.
%+ Stempeutics Research Private Limited, Akshay Tech Park, Whitefield, Bangalore 560066, India
Stempeutics Research Malaysia Sdn. Bhd., Technology Park, Malaysia 57000 Kuala Lumpur, Malaysia



%0 Journal Article
%A Goldring, Mary B.
%A Goldring, Steven R.
%D 2010
%T Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis
%J Annals of the New York Academy of Sciences
%V 1192
%N 1
%P 230-237
%8 关节软骨和软骨下骨在骨关节炎的发病机制
%! Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis
%@ 1749-6632
%R 10.1111/j.1749-6632.2009.05240.x
%K osteoarthritis
articular cartilage
calcified cartilage
bone adaptation
subchondral bone
%< 1.大聚集蛋白聚糖,aggrecan,除了许多其他分子包括小蛋白聚糖。 II型胶原原纤维的胶原纤维 
%U http://dx.doi.org/10.1111/j.1749-6632.2009.05240.x
http://onlinelibrary.wiley.com/store/10.1111/j.1749-6632.2009.05240.x/asset/j.1749-6632.2009.05240.x.pdf?v=1&t=hvx2kqto&s=18454cd8f24b88508de6f43a593959ce0ef4fd1e
%> internal-pdf://Goldring-2010-Articular cartilage-3444892928/Goldring-2010-Articular cartilage.pdf



%0 Journal Article
%A Soltanoff, C. S.
%A Chen, W.
%A Yang, S.
%A Li, Y. P.
%D 2009
%T Signaling Networks that Control the Lineage Commitment and Differentiation of Bone Cells
%J Critical Reviews in Eukaryotic Gene Expression
%V 19
%N 1
%P 1-46
%! Signaling Networks that Control the Lineage Commitment and Differentiation of Bone Cells
%Z Crit Rev Eukar Gene
%@ 1045-4403
%M WOS:000263092700001
%K osteoblasts
osteoclasts
signaling pathways
transcriptional regulation
skeletal disease
bone genes
nf-kappa-b
colony-stimulating factor
transcription factor pu.1
growth-factor-beta
activated protein-kinase
osteoclast-associated receptor
sympathetic-nervous-system
mesenchymal stem-cells
cytokine-mediated osteoclastogenesis
inhibits osteoblast differentiation
%X Osteoblasts and osteoclasts are the two major bone cells involved in the bone remodeling process. Osteoblasts are responsible for bone formation while osteoclasts are the bone-resorbing cells. The major event that triggers osteogenesis and bone remodeling is the transition of mesenchymal stem cells into differentiating osteoblast cells and monocyte/macrophage precursors into differentiating osteoclasts. Imbalance in differentiation and function of these two cell types will result in skeletal diseases such as osteoporosis, Paget's disease, rheumatoid arthritis, osteopetrosis, periodontal disease, and bone cancer metastases. Osteoblast and osteoclast commitment and differentiation are controlled by complex activities involving signal transduction and transcriptional regulation of gene expression. Recent advances in molecular and generic studies using gene targeting in mice enable a better understanding of the multiple factors and signaling networks that control the differentiation process at a molecular level. This review summarizes recent advances in studies of signaling transduction pathways and transcriptional regulation of osteoblast and osteoclast cell lineage commitment and differentiation. Understanding the signaling networks that control the commitment and differentiation of bone cells will not only expand our basic understanding of the molecular mechanisms of skeletal development but will also aid our ability to develop therapeutic means of intervention in skeletal diseases.
%Z 403OU
Times Cited:26
Cited References Count:390
%< 1.成骨细胞的信号网络图（有意义）
%U <Go to ISI>://WOS:000263092700001
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392028/pdf/nihms219131.pdf
%> internal-pdf://Soltanoff-2009-Signaling Networks t-2019164416/Soltanoff-2009-Signaling Networks t.pdf
%+ Li, Yp
Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA
Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA
Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA
Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA
%G English



%0 Journal Article
%A de Crombrugghe, B.
%A Lefebvre, V.
%A Nakashima, K.
%D 2001
%T Regulatory mechanisms in the pathways of cartilage and bone formation
%J Curr Opin Cell Biol
%V 13
%N 6
%P 721-7
%8 监管机制在软骨和骨形成的途径
%! Regulatory mechanisms in the pathways of cartilage and bone formation
%Z Current opinion in cell biology
%@ 0955-0674 (Print)
0955-0674 (Linking)
%M 11698188
%K Animals
Bone and Bones/*embryology
Cartilage/*embryology
Cell Differentiation
Chondrocytes/physiology
*Chondrogenesis
Growth Plate/anatomy & histology/embryology
Humans
Mesoderm/physiology
Mice
Models, Biological
*Osteogenesis
Signal Transduction
Transcription Factors/physiology
%X Three transcription factors of the Sox family have essential roles in different steps of the chondrocyte differentiation pathway. Because the transcription factor Cbfa1, which is needed for osteoblast differentiation, also stimulates hypertrophic chondrocyte maturation, it links the chondrocyte and osteoblast differentiation pathways in endochondral bone formation. Signaling molecules, including Indian Hedgehog, PTHrP and FGFs, also establish essential links either between these pathways, between steps in these pathways or between signaling molecules and transcription factors, so that a more comprehensive view of endochondral bone formation is emerging.
%Z de Crombrugghe, B
Lefebvre, V
Nakashima, K
eng
AR 42919/AR/NIAMS NIH HHS/
AR 46249/AR/NIAMS NIH HHS/
Research Support, U.S. Gov't, P.H.S.
Review
2001/11/08 10:00
Curr Opin Cell Biol. 2001 Dec;13(6):721-7.
%U http://www.ncbi.nlm.nih.gov/pubmed/11698188
%+ The University of Texas M.D. Anderson Cancer Center, Department of Molecular Genetics, 1515 Holcombe Boulevard, Box #11, Houston, Texas 77030, USA. bdecromb@mdanderson.org



