Spring 2007 Bone Seminar Series

Tuesday, February 6, 2007

Speaker: Gerard Karsenty, MD, PhD, Paul A. Marks Professor; Chairman, Department of Genetics and Development, Columbia University

Host: X. Edward Guo, PhD, Columbia University

Topic: Genetic Control of Bone Mineralization

Dr. Karsenty’s Research Interests: Genetic control of skeletal development and physiology

Abstract
We have been studying the genetic control of extracellular matrix mineralization for the last 12 years. Our main question is why are the genes involved in the initiation of this process and why is it restricted to bone? Through the analysis of a mutant mouse strain we generated in the lab, the mice lacking matrix Gla protein, we came to realize that bone—like ECM mineralization—can occur in absence of osteoblasts. This observation challenged the concept that bone mineralization occurs because of the presence of specific genes in osteoblasts. This led us to revisit in cell culture and mostly in vivo the role of the various genes that could be involved in bone mineralization. We also in the meantime revisited some aspects of rickets. Our results indicate that to initiate mineralization of the bone ECM and to restrict it to this ECM, Nature uses a relatively cheap and trivial trick: it relies on the coexpression in osteoblasts only of genes that otherwise are more broadly expressed. A more recent analysis of a mouse model of a human disease brought further support to this concept.

Tuesday, March 13, 2007

Speaker: Susannah P. Fritton, PhD, Associate Professor, Department of Biomedical Engineering, City College of New York

Host: Robert Majeska PhD, Mount Sinai School of Medicine

Topic: Bone as a Sponge: Where Does the Fluid Flow?

Confocal microscopic image of the
lacunar-canalicular space surrounding an osteocyte

Dr. Fritton’s Research Interests: Understanding the adaptive response of bone to mechanical forces; bone's mechanosensory system

Abstract
Interstitial fluid flow around osteocytes is believed to be important for enabling metabolic survival of the osteocyte as well as for providing a mechanical stimulus to the cell. Our recent work examines the role of bone microstructure in interstitial fluid flow. This work has involved using molecular tracers in vivo to delineate the pore size of the fiber matrix that surrounds the osteocyte in the lacunar-canalicular porosity. We have also used confocal microscopy to better quantify bone microstructural features such as osteocyte lacunar size and three-dimensional distribution of the canaliculi. In addition, because it has been proposed that an alteration in osteocyte viability due to osteoporosis could alter the interconnectedness of the osteocyte network, we have recently analyzed the lacunar-canalicular porosity of both normal and osteoporotic bone using high-resolution images that demonstrate bone's microstructural details. Together these studies are helping to elucidate the pathways of interstitial fluid flow so that we can better understand the mechanical stimulus experienced by bone cells.

Tuesday, April 17, 2007

Speaker: Cristina C. Teixeira, DMD, MS, PhD, Assistant Professor, Department of Basic Science and Craniofacial Biology and Department of Orthodontics, New York University College of  Dentistry

Host: Adele Boskey, PhD, Hospital for Special Surgery

Topic: Lessons from Growth Plate Biology: New Approaches to Osteoarthritis and Bone Tissue Engineering

Dr. Teixeira’s Research Interests: Endochondral bone formation, engineering growing bone and osteoarthritis. My recent work focuses on the role of nitric oxide and the cGMP pathway on chondrocyte hypertrophy.

Abstract
There are two types of cartilage, permanent and transient. While having the same embryonic origin they fulfill different functions and have different fates. Articular and tracheal cartilage are classified as permanent and persist throughout life. Most of the embryonic skeleton, the growth plates of long bones, the callus formed at fracture sites, and the tissue created during distraction osteogenesis consist of transient cartilage. This transient cartilage signals its gradual replacement by bone during the process of endochondral bone formation. In the past decade I have been studying the cellular and molecular biology of chondrocyte differentiation, maturation, and apoptosis during endochondral bone formation. In this presentation, I will discuss some of our findings in the growth plate and propose new research approaches to the fields of osteoarthritis and bone tissue engineering.

Tuesday, May 15, 2007

Speaker: Shannon McFarlin, PhD, Postdoctoral Associate, Department of Anthropology and the Center for the Advanced Study of Hominid Paleobiology, The George Washington University

Host: Timothy G. Bromage, PhD, New York University College of Dentistry

Topic: Ontogenetic Variability in Primary Bone Microstructure of Old World Monkeys and Apes

Dr. McFarlin’s Research Interests: Comparative primate skeletal biology and microanatomy and their significance for interpreting the growth and life history, environment, and functional biology of modern and fossil forms; bone growth and development; hominoid evolution and paleobiology

Abstract
The heterogeneous appearance of bone in cross section is hypothesized to reflect the influence of variability in bone depositional rates during ontogeny and functional loading during life. A major focus of prior research on bone microstructure in primates has been its biomechanical significance and/or species’ patterns of secondary remodeling. Little is known concerning ontogenetic variability in bone microstructure. Further, the organization and distribution of primary bone tissues formed during the growth process has been surprisingly unexplored. Such information is important not only for understanding adult bone structure; it also has the potential to yield valuable insight into studies of the life history and functional biology of humans and other primates.

As part of a larger ongoing effort to systematically characterize bone microstructure in primates, the research to be presented examines ontogenetic and regional variability in primary bone tissues in three species of Old World monkeys and apes differing in life history and locomotor behavior. Undemineralized thin sections from the midshaft femur and humerus were imaged in brightfield and circularly polarized light microscopy. From these same field-of-view images, tissue type maps were created for the quantification of primary tissue type proportions determined within whole cross sections and among bone regions. Variability in primary bone microstructure was considered within the context of local growth and secondary remodeling history.

Results demonstrated significant ontogenetic variability in primary tissue type proportions. Vascular fibrolamellar tissues were observed during early ontogeny, while increased proportions of lamellar bone reflect declining growth rates during later ontogeny. Interestingly, taxa differed in the timing of this transition and the particular primary tissue types observed, in accordance with species differences in postnatal growth patterns. Qualitative observations revealed that more subtle changes in bone depositional rates during ontogeny may also be discriminated from features not measured, such as vascular patterns, growth arrest lines, and collagen fiber orientation of primary bone. These data provide important baseline information concerning ontogenetic and regional variability in the bone microscopic structure of primates, and they establish a comparative foundation for extending analyses to paleontological contexts.