CBS Emeritus Office: 3472

• DVM, Purdue University
• PhD, University of Minnesota

Orthopedics; Cellular mechanisms of bone elongation; Contemporary microscopical techniques; Research ethics;

We are interested in bone growth in children and adolescent animals. We study the cellular mechanisms and their controls by which growth plates condrocytes achive bone elongation.

In many ways all growth plates are similar regardless of species or anatomical location. In any given growth plate, chondrocytes occur in a characteristic spatial organization that also is a representation of the temporal progression of individual chondrocytic differentiation. We are interested in understanding the chondroctyic differentiation cascade in relationship to growth. Here our objective is to understand the interrelationships 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 all growth plates are different. When we go from the perspective of discrete events and regulatory gates to rates of transitions (rate of change), growth rates are not uniform. but vary from one growth plate to the next, depending on species, age and anatomical location: Growth plates are all different. Growth plates even on opposite ends of the same bone in the same individual, grow at rates that may differ by a factor of 3X. This phenomenon - differential growth - is a hallmark of growth plate biology. Differential growth describes the unique rate and duration of growth of different growth plates. In addition to understanding how regulatory molecules or regulatory stressors act to achieve growth, we also are interested in which of these factors act locally such that rates of growth vary.

Our current interest is focused on biomechanical signals. Our current experimental approach involves the implantation of microtransducers in adolescent lambs to measure growth precisely. While it is possible to study the chondrocytic differentian cascade and the sequence of gene expressing in vitro, growth (like heat) is an example of an emerging propertry of a complex system and therefore it can nly be studied in vivo. We also use an approach of quantitative measurement of multiple chondrocytic kinetic parameters that describe the dynamics of cellular contributions to growth. We analyze perturbations of growth with the intent of designing and implementing optimal strategies for managing the correction of abnormalities of long bone growth.

Current Funding: The Hypertrophy Chondrocytes and its Pericellular Matrix. NIH. $962,950 total 5 year direct costs. Principal Investigator 7/1/99 to 6/30/05.

Professor
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
• stereology

Bernardini, E. S., C.E. Farnum, E. Leiferman, and N.J. Wilsman 2005 Differential growth among growth plates in fetal, neonatal, and adolescent rats: A Metric and stereologic analysis of emergence and mechanism. (in preparation)

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

Wilsman, N.J., C.E. Farnum, E.M. Leiferman, and M. Lampl 1999 Growth plate biology in the context of growth by saltations and stasis. In: Saltation Stasis and Human Growth and Development: Evidence, Methods, and Theory. ed. M. Lampl Smith-Gordon, Philadelphia, 71-87.

Farnum, C.E., and N.J. Wilsman 1998 Effects of Distraction and Compression on growth plate function. In: Advances in the Basic and Clinical Understanding of the Growth Plate,eds. J. Buckwalter and H.C. Andersen, American Academy of Orthopaedic Surgeons, Chicago, 517-532.

Wilsman, N.J., and C.E. Farnum 1998 Growth plate cellular function, In: Advances in the Basic and Clinical Understanding of the Growth Plate, eds. J. Buckwalter and H.C. Andersen, American Academy of Orthopaedic Surgeons, Chicago, 203-224.

Wilsman, N.J., C.E. Farnum, E.M. Green, E.M. Leiferman, and M.K. Clayton 1996 Cell cycle analysis of proliferative zone chondrocytes in growth plates elongating at different rates. J. Orthop. Res., 14: 562-572.Abstract

Wilsman, N.J., C.E. Farnum, E.M. Leiferman, M. Fry, and C Barreto 1996 Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J. Orthop. Res., 14:927-936. Abstract

Barreto, C., and N.J. Wilsman 1994 Hypertrophic chondrocyte volume and growth rates in avian growth plates. Res. Vet. Sci., 56: 53-61.

Breur, G.J., J. Turgai, B.A. VanEnkevort, C.E. Farnum, and N.J. Wilsman 1994 Stereological and serial section analysis of chondrocytic enlargement in the proximal tibial growth plate of the rat. Anat. Rec., 239: 255-268.

Barreto, C., R.M. Albrecht, D.E. Bjorling, R.J. Horner, and N.J. Wilsman 1993 Evidence of the growth plate and the growth of long bones in juvenile dinosaurs. Science, 262: 2020-2023.

Farnum, C.E., and N.J. Wilsman 1993 Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine. Calcif. Tiss. Int., 52: 110-119.

Breur, G.J., B.A. VanEnkevort, C.E. Farnum, and N.J. Wilsman 1992 Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. Year-Book of Orthopaedics, Mosby, Chicago.

Farnum, C.E., K. Jones, R.Riis, and N.J. Wilsman 1992 Ocular-chondrodysplasia in Labrador Retriever dogs: A morphometric and electron microscopical analysis. Calcif. Tiss. Int., 50: 564-572.

Breur, G.J., C.E. Farnum, G.A. Padgett, and N.J. Wilsman 1992 Cellular basis of decreased rate of longitudinal bone growth in pseudoachondroplastic dogs. J. Bone Jt. Surg., 74-A: 516-528.

Breur, G.J., B.A. VanEnkevort, C.E. Farnum, and N.J. Wilsman 1991 Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. J. Orthop. Res., 9: 348-359.

Farnum, C.E., J.A. Turgai, and N.J. Wilsman 1990 Visualization of living terminal hypertrophic chondrocytes of growth plate cartilage in situ by rectified interference contrast microscopy and time lapse cinematography. J. Orthop. Res., 8; 750-763.