Department of Comparative Biosciences
Titles and Education
- DVM, Purdue University
- PhD, University of Minnesota
Orthopedics; Cellular mechanisms of bone elongation; Contemporary microscopical techniques; Research ethics;
Our lab is interested in bone growth in children and adolescent animals. We study the cellular mechanisms and their controls by which growth plate chondrocytes achieve bone elongation.
In many ways all growth plates are similar regardless of species or anatomical location. In all growth plates, chondrocytes occur in a characteristic spatial organization that also is a representation of the temporal progression of individual differentiation. We are interested in understanding the chondrocytic differentiation cascade in relationship to growth. Here our objective is to understand the relationships among multiple controls, acting through systemic, paracrine, and autocrine mechanisms that are responsible for coordinated long bone growth from embryonic life through adolescence.
When, however, we add kinetics to our consideration of growth plate biology, and we considerer growth plates not at the cellular level but at the level of the individual, we find that growth plates have a unique growth velocities. Growth plates even on opposite ends of the same bone in the same individual at the same moment in time, have growth velocities that may differ by a factor of 3X. This phenomenon - differential growth - is a hallmark of growth plate biology. Many of our studies incorporate chondrocytic kinetics and to do this we need to incorporate an element of time. Many of our studies is to use fluorochrome labeling to measure elongation per day, and more recently we have been using microtransducers to measure growth velocity on a minute by minute basis. Our current interest is focused on biomechanical signals.
Our experimental and dynamic studies have documented the robust nature of the growth plate. The growth plate has (at least) two engines that power and control velocity; these sometimes appear to be coupled and sometimes they appear to operate in parallel. Depending on the situation, either proliferation kinetics or volume increase kinetics can be turned up or turned down to meet the demands of the individual for normal growth velocity, with more subtle tuning resulting from concomitant matrix remodeling. Under some conditions one predominates, but under many conditions the two appear to be coupled, demonstrating that the system has redundancy, and that total failure is unlikely.
Our studies also emphasize that the growth plate probably operates under the laws of non-linear dynamical systems with growth (like heat) is an emerging property of an increasingly complex system. As such, a single variable or even multiple variables can reasonably wax and wane without affecting normal growth velocity. To understand the effect of such a factor, at some point that factor must be tested in the context of all other factors while measuring the dynamics of the system. Our studies go beyond demonstrating, what has long been obvious, that it is important to measure growth plate dynamics in time frames significantly shorter than once a year (as our parents did for us as children when they backed us up to the doorframe to pencil in our incremental height gain over the last twelve months), or even weeks, which is the time frame traditionally used for monitoring the results of clinical interventions. Results of our studies demonstrate that analyses of growth plate dynamics measured in time frames as short as minutes allow one to start to understand the total complexity of responsiveness of the chondrocytic differentiation cascade during postnatal endochondral ossification.
Current and Recent Funding:
N.I.H. NAIMS, RO1-35155 – 18 “The Hypertrophic Chondrocyte and its Pericellular Matrix” Role: Principal Investigator, 06/01/1988 — 10/01/2006
Biomet Corporation, “Comparing the Classic and the Biomet Growth Plate: Which is More Efficient at Altering Growth and Do Mechanisms of Growth Differ?” Co-Principal Investigator, 7-1-07 to 10-1-08
Department of Pediatrics Research and Development Award. (Noonan, Conway co-PI) 02/01/06-Present “Flouroquinolones, Do they affect growth.” Jim Conway (pediatric infectious diseases), Paul Hutson (pharmacy) and Norman J. Wilsman, Consultants
Department of Orthopaedics, University of Wisconsin (Noonan PI) “Evaluation of the 8-Plate Hemiepiphyseal Staple on Human Growth” Collaborator – Stereology Consultant. 06/01/06 — Present
N.I.H. NIDDK RO1 (Sanchez MD, PI) “Regulation of Skeletal Growth in Renal Failure”. Consultant, 07/01/05 — 06/30/10
- Associate Dean for Research and Graduate Training, (1993 - 2000)
- Fundamental principles of veterinary anatomy 934:500
- non-linear dynamics of physiological systems
- research ethics
- contemporary microscopical techniques
White, J.R., N.J Wilsman, E. Leiferman, and K.J. Noonan 2009 Histomorphometric analysis of an adolescent distal tibial physis prior to growth plate closure. J. Ped. Orthop. (in press)
Sansone, J.M., N.J Wilsman, E. Leiferman, and K.J. Noonan 2009 The effect of periosteal resection on tibial growth velocity measured by microtransducer technology in lambs. J Ped. Orthop. 29: 61-67.
Wilsman, N.J. E. Bernardini, E. Leiferman, K.J. Noonan, and C.E. Farnum 2008 Age and pattern of the onset of differential growth among growth plates in rats. J. Orthop. Res 26: 1457-1465
Grover, J.P., Vanderby, R, Leiferman, E.M., Wilsman, N.J., and Noonan, K.J. 2007 Mechanical Behavior of the Lamb Growth Plate in Response to Asymmetric Loading: A Model for Blount's Disease. J. Ped. Orthop., 27:485-492
Noonan, K.J., C. E. Farnum, E.M. Leiferman, M. Lampl, M.D. Markel & N. J. Wilsman 2004 Growing Pains: Are they due to increased growth during recumbency as documented in a lamb model? Pediatric Orthopedics, 24: 726-731.
Sanchez, C.P., H. Yu-Zhu, E. Leiferman, and N.J. Wilsman 2004 Bone Elongation in Rats with Renal Failure and Mild or Advanced Secondary Hyperparathyroidism. Kidney International, 65: 1740 - 1748. Abstract
Farnum, C.E., Lee, A.O., O'Hara, K. and Wilsman, N.J. 2003 Effect of short-term fasting on bone elongation rates: an analysis of catch-up growth in young male rats. Pediatric Research 53:33-41.Abstract
Farnum, C.E. and Wilsman, N.J. 2002 Chondrocyte kinetics in the growth plate. In: The Growth Plate. Edited by Irving M. Shapiro, Barbara Boyan and H. Clarke Anderson. IOS Press, Washington D.C. pp.245-257.
Farnum, C.E., A. Nixon, A.O. Lee, D.T. Kwan, L. Belanger and N.J. Wilsman 2001 Converting a differential cascade into longitudinal growth: stereology and analysis of transgenic animals as tools for understanding growth plate function. Current Opinions in Orthopaedics 12: 428 – 433.
Farnum, C.E., A. Nixon, A.O. Lee, D.T. Kwan, L. Belanger and N.J. Wilsman 2000 Quantitative three dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate, Cells, Tissues and Organs. 167: 247-258. Abstract