Bone growth in children occurs by endochondral ossification in cartilaginous growth plates at the ends of long bones. 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. This research focuses on understanding the chondrocytic differentiation cascade in relationship to growth. The long term 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, and to analyze perturbations of growth with the intent of designing and implementing optimal strategies for managing the correction of abnormalities of long bone growth. Using an approach of quantitative measurement of multiple chondrocytic kinetic parameters that completely describe the dynamics of cellular contributions to growth, the Specific Aims of the current proposal are: To test the hypothesis that patterns of differential growth characteristic of specific bones are absent prenatally, but are established starting in the perinatal period and become well defined during early postnatal development, and that this translation is reflected in different cellular control mechanisms; To test the hypothesis that postnatal bone elongation occurs by a pattern of brief intense growth saltations followed by much longer periods of no growth (stasis); To test the hypothesis that the primary action of growth hormone, either circulating systemically or delivered locally, is to increase all rate-dependent phases of chondrocytic differentiation during the postnatal period, thus accelerating rates of differential growth and increasing growth velocity; To test the hypothesis that decreased rate of growth following minimal total nutritional deprivation postnatally, as well as catch-up growth following return to normal nutritional status, are controlled through altering the rate at which chondrocytes at all levels of the growth plate proceed through the differentiation cascade, amplified by volume changes at the level of the hypertrophic chondrocyte.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035155-16
Application #
6511675
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Sharrock, William J
Project Start
1985-07-01
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
16
Fiscal Year
2002
Total Cost
$228,893
Indirect Cost
Name
University of Wisconsin Madison
Department
Biology
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Sansone, Jason M; Wilsman, Norman J; Leiferman, Ellen M et al. (2009) The effect of periosteal resection on tibial growth velocity measured by microtransducer technology in lambs. J Pediatr Orthop 29:61-7
Sansone, Jason M; Wilsman, Norman J; Leiferman, Ellen M et al. (2009) The effect of fluoroquinolone antibiotics on growing cartilage in the lamb model. J Pediatr Orthop 29:189-95
Wilsman, Norman J; Bernardini, Elizabeth S; Leiferman, Ellen et al. (2008) Age and pattern of the onset of differential growth among growth plates in rats. J Orthop Res 26:1457-65
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Farnum, C E; Nixon, A; Lee, A O et al. (2000) Quantitative three-dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate. Cells Tissues Organs 167:247-58
Bailon-Plaza, A; Lee, A O; Veson, E C et al. (1999) BMP-5 deficiency alters chondrocytic activity in the mouse proximal tibial growth plate. Bone 24:211-6
Wilsman, N J; Farnum, C E; Leiferman, E M et al. (1996) Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J Orthop Res 14:927-36
Wilsman, N J; Farnum, C E; Green, E M et al. (1996) Cell cycle analysis of proliferative zone chondrocytes in growth plates elongating at different rates. J Orthop Res 14:562-72

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