Begell House Inc.
Critical Reviews™ in Eukaryotic Gene Expression
CRE
1045-4403
17
2
2007
Molecular Signaling in Bone Regeneration
87-102
10.1615/CritRevEukarGeneExpr.v17.i2.10
H.
Bahar
Department of Oral Biology, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Dafna
Benayahu
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Israel
A.
Yaffe
Haddasah School of Dental Medicine, Hebrew University, Jerusalem 91120, Israel
I.
Binderman
Department of Oral Biology, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Regeneration is the ability of cells to restore lost or damaged tissues and organs in adults by pathways that mimic developmental processes. Although many of the molecular mechanisms that control cellular differentiation and growth during embryogenesis recur during fracture healing, these processes take place in a postnatal environment that is unique and distinct from those that exist during embryogenesis. Bone tissue has a remarkable capacity of regeneration without scarring. This article highlights central biological and molecular processes that are crucial in embryonic bone development. Several animal bone regeneration models are described. The patterns of gene expression during the regeneration process in the different models are reviewed. Exploring the similarities and the differences in the molecular processes in different models will contribute to the understanding of their potential in the processes of bone regeneration and tissue engineering.
Insights on the Functional Role of Chromatin Remodelers in Osteogenic Cells
103-113
10.1615/CritRevEukarGeneExpr.v17.i2.20
Dafna
Benayahu
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Israel
Nitsan
Shacham
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Israel
Irena
Shur
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Israel
Control of eukaryotic gene expression requires interaction between sequence-specific transcription factors and their regulatory elements on the particular promoter. The dynamic alteration of chromatin structure regulates the accessibility of these elements in the genome and therefore contributes to the control of transcrip-tional activity. Here we discuss chromatin remodelling in the context of osteoblast lineage regulation. This review specifically highlights the role of the protein chromatin-related mesenchymal modulator (CReMM/CHD9), a recently identified chromatin remodeler, in osteogenic cell differentiation.
Vitamin D Modulation of the Activity of Estrogenic Compounds in Bone Cells In Vitro and In Vivo
115-148
10.1615/CritRevEukarGeneExpr.v17.i2.30
Dalia
Somjen
Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Vitamin D analogs modulate different organs, including modulation of energy metabolism, through the induction of creatine kinase (CK) activity. Skeletal organs from vitamin D-depleted rats showed lower constituent CK than those from vitamin D-replete rats. Moreover, estradiol-17β (E2) or dihydrotestosterone (DHT), which increased CK in organs from intact female or male rats, respectively, stimulated much less CK in vitamin D-depleted rats. Treatment of intact female rats with noncalcemic vitamin D analogs significantly upregulated E2- and DHT-induced CKresponse. These analogs upregulated the CK response to selective estrogen receptor modulators (SERMs) in organs from intact or ovariectomized (Ovx) female rats but abolished SERMs' inhibitory effect on E2-induced CK. These analogs significantly increased estradiol receptor α (ERα) protein in skeletal organs as well as histomorphological and biochemical changes due to this treatment followed by E2 or DHT. The analogs alone markedly altered the growth plate and the trabeculae and increased trabecular bone volume (%TB V) and trabecular width. The addition of E2 or DHT to this treatment restored all parameters as well as increased %TBV and cell proliferation. Treatment of Ovx female rats with JK 1624 F2-2 (JKF) decreased growth-plate width and increased %TB V, whereas QW1624 F2-2 (QW) restored growth-plate width and %TB V. Treatment of E2 with JKF restored %TBV and growth-plate width, whereas E2 with QW restored all parameters, including cortical width. There was also upregulation of the response of CK to E2 in both combined treatments. Our human-derived osteoblast (hObs)-like cell cultures respond to estrogenic compounds, and pretreating them with JKF upregulated the CK response to E2, raloxifene (Ral), and some phytoestrogens. ERα and ERβ proteins, as well as mRNA, were modulated by CB 1093 (CB) and JKF. JKF increased specific nuclear E2 binding in female hObs but inhibited specific membranal E2 binding. hObs express 25 hydroxyvitamin D3-1α hydroxylase (1-OHase)-mRNA and its biological activity, which are both modulated by parathyroid hormone (PTH) and estrogenic compounds. Our results demonstrate mutual interaction between vitamin D and estrogenic compounds. We therefore conclude that combined treatment with less-calcemic analogs of vitamin D and estrogenic compounds might be superior for treatment of bone damage caused by ovariectomy in female rats, with possible application for postmenopausal osteoporosis.
Responsiveness of Osteoblastic and Osteolytic Bone Metastases to Vitamin D Analogs
149-158
10.1615/CritRevEukarGeneExpr.v17.i2.40
Sara
Peleg
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas, M. D. Anderson Cancer Center, Houston, TX
Bone is the primary site of metastases in advanced androgen-independent prostate cancer. These metastases are primarily bone-forming, although the presence of osteolytic response has also been reported. Bone-homing therapy is a strategy based on the popular seed-and-soil relationship between the epithelial malignant cells and the bone stroma. Calcitriol (1,25-dihydroxyvitamin D3) and its synthetic analogs (deltanoids) are drugs that have a direct effect on both the skeleton and the invading metastatic cells and, therefore, are considered useful in the treatment of advanced prostate cancer. In this article, I review the nature of the response induced by the malignant cells in the bone (bone formation or bone resorption) and how it affects the outcome of a vitamin D analog treatment in preclinical models of metastatic bone disease.
Heparan Sulfate Control of Proliferation and Differentiation in the Stem Cell Niche
159-172
10.1615/CritRevEukarGeneExpr.v17.i2.50
Victor
Nurcombe
Institute of Molecular and Cell Biology; and Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Simon M.
Cool
Institute of Molecular and Cell Biology; and Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Tissue-specific stem cell populations are established in "niches," anatomic locations with precise biochemical and cellular configurations that regulate their release and participation in tissue generation, maintenance, and repair. Niches have evolved to protect and perpetuate the self-renewing, undifferentiated state of the cells within and to regulate the rate of production of committed, tissue-specific progenitors. A niche thus integrates the cell growth, cell adhesion, and cell-cell signals that mediate the balanced response of stem cells to the needs of the organism. One constituent of every niche with the capacity to mediate almost all of the required functions is the glycosaminoglycan sugar heparan sulfate. This sugar is a master regulator of mitogenic and adhesive molecule behavior with the ability to rapidly change its binding affinities on the cell surface. Its properties may be the key to understanding the interplay between stem cells and their niche that creates the dynamic system necessary for sustaining tissues. As such, it has great promise for the design of tissue-specific stem cell therapeutics.