Cellular and Molecular Biology of Bone

Masaki Noda

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9780125202251
• eBook ISBN: 9780080925004
• Topic: Biological Sciences
• Subtopic: Physiology
• Index: Biological Sciences

Written by well-known experts in their respective fields, this book synthesizes recent work on the biology of bone cells at the molecular level. Cellular and Molecular Biology of Bone covers the differentiation of these cells, the regulation of their growth and metabolism, and their death resorption. The authors' special comprehensive treatment of the cellular and molecular mechanisms of bone metabolism makes this book a unique and valuable tool. Cellular and Molecular Biology of Bone provides interested readers-with concise state-of-the-art reviews in bone biology that will enlarge their scope and increase their appreciation of the field. Research in this area has intensified recently due to the increasing incidence of osteoporosis. The editor hopes an understanding of the basic biology of this disease will prove relevant to its prevention and treatment.

1

OSTEOBLASTIC CELL LINEAGE

JANE E. AUBIN, KURSAD TURKSEN and JOHAN N.M. HEERSCHE

Publisher Summary

This chapter provides an overview of the osteoblast lineage and discusses the possibilities for recognizing stages of differentiation or maturity. Bone formation takes place in the organism during embryonic development, growth, remodeling, and fracture repair and when induced experimentally, for example, by the implantation of decalcified bone matrix or purified or recombinant members of the bone morphogenetic protein family. Based on morphological and histological studies, osteoblastic cells are categorized in a presumed linear sequence progressing from osteoprogenitor to preosteoblasts, to osteoblasts, and then to lining cells or osteocytes. A major challenge in the field of osteoblast differentiation is to recognize unambiguously cells at different stages of differentiation or maturation. Individual cells within osteoblastic clonal cell lines stain with different intensities, and staining is completely absent in other well-characterized lines by these different antibodies; comparing these patterns to staining patterns of bone tissue should help in discriminating stages in this lineage.

I Introduction

II Cells of the Osteoblast Lineage

A General Morphological and Histological Definition

B Osteoblast Phenotypic Expression and Osteoblast Markers

III Origin and Lineage of the Osteoblast

A Mesenchymal Stem Cells and Multipotential and Restricted Progenitors

B Osteo-Chondroprogenitors

IV Osteoblast Heterogeneity: Subpopulations, Stages of Differentiation, or Aberrant Expression in Vitro?

V Indirect Identification of the Osteoprogenitor Cell

A Bone Formation in Vitro

B A Colony Assay for the Quantification of Osteoprogenitor Cells and Assessment of Their Proliferative and Self-Renewal Capacity

C Regulation of the Osteoprogenitors

VI Monoclonal Antibodies for Identification of Cells in the Osteoblast Lineage

VII Concluding Remarks

References

I INTRODUCTION

Bone formation takes place in the organism during embryonic development, growth, remodeling, and fracture repair and when induced experimentally—for example, by the implantation of decalcified bone matrix or purified or recombinant members of the bone morphogenetic protein family (Reddi, 1985; Urist, 1989; Wozney et al., 1990; Wozney, 1992). There is clearly a large reservoir of cells in the body capable of osteogenesis throughout life. During the past decade, new methods have been developed to study the cell biology of bone and gain insight into the various cell types important in bone function (for reviews, see Rodan and Rodan, 1984; Nijweide et al., 1986, 1988; Heersche and Aubin, 1990; Aubin et al., 1990b). It has also become increasingly clear that the metabolic activities of bone are under the control of a large number of systemic and local factors (Martin et al., 1987; Stern, 1988; Marcus, 1988; Martin, 1989; Mundy, 1989). Despite these advances, many questions remain. For example, detailed knowledge of the lineage of the osteoblast, including identification of transitional steps from stem cell to committed osteoprogenitor to osteoblast, interactions of cells within the lineage, and identification and regulation of stem cells and different levels of committed progenitors, is largely lacking. This chapter provides a review of the osteoblast lineage and possibilities for recognizing stages of differentiation or maturity. As such, it reviews current concepts of the origin, lineage, and differentiation of osteoblasts and currently available tools to study them, with emphasis on in vitro model systems.

II CELLS OF THE OSTEOBLAST LINEAGE

A General Morphological and Histological Definition

Based on morphological and histological studies, osteoblastic cells are categorized in a presumed linear sequence progressing from osteoprogenitor to preosteoblasts, to osteoblasts, and then to lining cells or osteocytes (Nijweide et al., 1986; Martin et al., 1987; Marks and Popoff, 1988; Bonucci, 1990; Wlodarski, 1990). Earlier morphological definitions of the active osteoblast as a cuboidal, polar, basophilic cell lining the bone matrix at sites of active matrix formation (Cameron, 1968; Holtrop, 1975) have been supplemented more recently by elucidation of their specific products—for example, type I collagen (Leblond, 1989), osteocalcin (Hauschka et al., 1989), osteopontin (SPP1) (Butler, 1989), and bone sialoprotein (Sodek et al., 1992a,b). Active osteoblasts give a strong histochemical reaction for alkaline phosphatase (APase) that disappears when cells cease their synthetic activity (Doty and Schofield, 1976) or become embedded in matrix as osteocytes (Holtrop, 1975). However, a number of criteria, such as morphology (Marotti, 1976; Villaneuva et al., 1981), biosynthetic activity detected by biochemical analysis (Otawara and Price, 1986), immunohistochemistry (Mark et al., 1988) or in situ hybridization (Heersche et al., 1992), suggest that newly differentiated osteoblasts (cuboidal, osteocalcin low or negative) differ from more mature osteoblasts later in their secretory lifetime (more flattened osteocalcin high). Thus, maturational stage—not only stage of differentiation—ultimately will have to be elucidated with these and other markers (see later).

In a region where osteoblasts are laying down bone matrix, the cuboidal cells directly behind them have been called preosteoblasts (Pritchard, 1952; Luk et al., 1974). Based on kinetic studies, it has been suggested that preosteoblasts are the precursors of the osteoblast in the regions of growing bone (Owen, 1963, 1967; Kember, 1971). Preosteoblasts morphologically resemble the osteoblast and show some markers of the osteoblast (e.g., APase activity [Doty and Schofield, 1976]), but they are clearly recognizably different from osteoblasts in not expressing others (see later). Other possibly earlier precursor cells may reside in the heterogeneous layer of proliferating cells behind the osteoblast/preosteoblast layer (Pritchard, 1972a,b). These earlier cells may be osteoprogenitor cells (Young, 1962). In addition to their position in the tissue near bone surfaces, osteoprogenitors are fibroblastic or spindle-shaped with oval or elongated nuclei and notable glycogen content (Scott, 1967). Their appearance and location in the tissues are the main criteria to define their presence. It seems likely, but there is no proof, that the farther away from the bone surface the osteogenic cell is the less differentiated it will be (Scott, 1967).

The osteocyte is considered the most mature or terminally differentiated cell of the osteoblast lineage (Jande and Belanger, 1973; Holtrop, 1975). Osteocytes are embedded in bone matrix occupying spaces (lacuanae) in the interior of bone and are connected to adjacent cells by cytoplasmic projections within channels (canaliculi) through the mineralized matrix (Menton et al., 1984). The presence of gap junctio...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• CONTRIBUTORS
• PREFACE
• Chapter 1: OSTEOBLASTIC CELL LINEAGE
• Chapter 2: MOLECULAR MECHANISMS MEDIATING DEVELOPMENTAL AND HORMONE-REGULATED EXPRESSION OF GENES IN OSTEOBLASTS: An Integrated Relationship of Cell Growth and Differentiation
• Chapter 3: CELLULAR AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR β
• Chapter 4: BONE MORPHOGENETIC PROTEINS AND THEIR GENE EXPRESSION
• Chapter 5: OUR UNDERSTANDING OF INHERITED SKELETAL FRAGILITY AND WHAT THIS HAS TAUGHT US ABOUT BONE STRUCTURE AND FUNCTION
• Chapter 6: MOLECULAR AND CELLULAR BIOLOGY OF THE MAJOR NONCOLLAGENOUS PROTEINS IN BONE
• Chapter 7: THE OSTEOCALCIN GENE AS A MOLECULAR MODEL FOR TISSUE-SPECIFIC EXPRESSION AND 1,25-DIHYDROXYVITAMIN D3 REGULATION
• Chapter 8: MOLECULAR MECHANISMS OF ESTROGEN AND THYROID HORMONE ACTION
• Chapter 9: RECENT ADVANCES IN THE BIOLOGY OF RETINOIDS
• Chapter 10: PARATHYROID HORMONE BIOSYNTHESIS AND ACTION: Molecular Analysis Of the Parathyroid Hormone Gene and Parathyroid Hormone/Parathyroid Hormone-Related Peptide Receptor
• Chapter 11: MOLECULAR MECHANISMS OF CALCITONIN GENE TRANSCRIPTION AND POST-TRANSCRIPTIONAL RNA PROCESSING
• Chapter 12: CYTOKINES IN BONE: Local Translators in Cell-To-Cell Communications
• Chapter 13: SIGNAL TRANSDUCTION IN OSTEOBLASTS AND OSTEOCLASTS
• Chapter 14: CELLULAR AND MOLECULAR BIOLOGY OF THE OSTEOCLAST
• Chapter 15: c-fos ONCOGENE EXPRESSION IN CARTILAGE AND BONE TISSUES OF TRANSGENIC AND CHIMERIC MICE
• Chapter 16: MOLECULAR BIOLOGY OF CARTILAGE MATRIX
• INDEX