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Molecular Biology in Orthopaedics

Posted on: Wednesday, 27 October 2004, 02:00 CDT

Molecular Biology in Orthopaedics Randy N. Rosier and Christopher H. Evans, editors. Rosemont, Illinois: American Academy of Orthopaedic Surgeons; 2003. 447 pages. $115.00 ($95.00 AAOS member).

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.

Lawrence Rosenberg, MD

The Journal of Bone and Joint Surgery

Needham, Massachusetts

Copyright Journal of Bone and Joint Surgery, Inc. Oct 2004

Source: Journal of Bone and Joint Surgery; American volume

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