During the last decade, phenomenal discoveries have been made in molecular
biology, and powerful new methods have been developed for elucidating the role
of abnormalities in gene expression in the pathogenesis of human diseases.
Scientists have appreciated the implications of these new developments. They
understand that we have entered a new era in biomedical research, and they
have applied this new knowledge and methodology in diverse areas of
orthopaedic research, particularly to studies of the biologic processes that
are involved in the formation of cartilage and bone during development and in
the repair of bone in the adult.
This excellent monograph provides extensive information regarding recent
developments in our understanding of the molecular biology of the
musculoskeletal system. The monograph is based on the proceedings of a
workshop called "Molecular Biology in Orthopaedics," which was
held in September 2001. More than fifty scientists who were engaged in
research in orthopaedic molecular biology presented reviews of the present
state of knowledge in particular areas and reported on the results of recent
studies in their own laboratories.
This monograph consists of thirty-four chapters, most of which are
extremely well written, extraordinarily informative, and a pleasure to read.
The editors are to be congratulated on their selection of the material
included in the monograph and their perceptive choice of authors, all of whom
prepared such superbly written, educational reviews. The workshop was
supported by the National Institute of Arthritis and Musculoskeletal and Skin
Diseases, the American Academy of Orthopaedic Surgeons, the Orthopaedic
Research and Education Foundation, and several private sponsors.
The monograph begins with an introduction describing the use of functional
genomic analysis to demonstrate abnormalities in the gene expression of
inflammatory mediators in osteoarthritic cartilage. Following the introduction
are sections on developmental biology, genetic diseases, tumors, molecular
biology of bone, molecular biology of cartilage, genetic animal models, and
gene therapy. In the section on developmental biology, the chapter entitled
"Bone Morphogenetic Proteins in Skeletal Development" provides a
foundation for the study of other chapters in this section, and might well be
read first. The chapter begins with a beautifully written description of the
initial events in skeletal development, and it considers the results described
in 126 relevant references, many of which pertain to studies carried out
between 1995 and 2000. The chapter entitled "Cellular Interactions and
Signaling in Skeletal Development" picks up where the aforementioned
chapter leaves off. This chapter focuses on the role of the Wnt family of
signaling molecules in the regulation of mesenchymal condensation and
chondrogenic differentiation, both of which occur during limb development.
In the chapter on transcriptional regulation of cartilage-specific genes,
the authors stressed that tissue-specific gene expression is regulated
predominantly at the initiation of transcription and requires the coordination
of a number of proteins that activate the transcriptional machinery. In the
section on the molecular biology of bone, two chapters—
"Transcriptional Control of the Osteoblast Phenotype," and
"RUNX2: An Organizer of the Transcriptional Regulatory Machinery for
Tissue-Specific Gene Expression"—focus on the regulation of
transcription in osteogenesis. The information and key references included in
the chapters described above provide a basis for understanding the
pathogenesis of orthopaedic diseases and for the development of new modalities
of treatment of these diseases. For example, in the section on genetic
diseases, in the chapter entitled "Fibrodysplasia Ossificans
Progressiva: Deciphering the Molecular Pathways of Ectopic
Skeletogenesis," the authors described studies to identify the genetic
basis of fibrodysplasia ossificans progressiva (FOP). In a recent study, the
authors and their collaborators have shown that gene transfer of a Noggin
mutein inhibits bone morphogenetic protein-4 (BMP-4) induced heterotopic
ossification in a mouse model of this disorder.
Other chapters focus on osteoclast biology, the molecular mechanisms
involved in osteoclastogenesis, the regulation of osteoclast activity, and the
mechanisms involved in the excessive osteoclast activity seen in pathologic
conditions associated with bone loss, such as rheumatoid arthritis and the
osteolysis that occurs as a result of aseptic loosening of orthopaedic
implants.
In summary, the concise, lucidly written chapters in this monograph provide
a remarkably comprehensive overview of the present state of knowledge
pertaining to the biology of the musculoskeletal system and the pathobiology
of orthopaedic diseases. The monograph should be useful to investigators who
are engaged in orthopaedic research as well as to readers who are interested
in the pathogenesis of orthopaedic diseases.