During endochondral ossification, chondrocytes of the cartilaginous growth plate are found in a spatial gradient of cellular maturation beginning with cellular proliferation and ending with cellular hypertrophy. The focus of this study is chondrocytic hypertrophy -- its contribution to overall bone growth during normal endochondral ossification, its significance in post-natal diseases of long bone growth, and its potential as a component of long bone growth which can be manipulated for the correction of angular deformities or limb anisomelia. The long term objective is to understand what controls the magnitude of chondrocytic hypertrophy as this relates to the rate of overall bone growth, as well as the control by these cells in directing the progress of metaphyseal cellular elements. This relates directly to an understanding of the pathogenesis of a wide variety of growth plate disorders characterized by both abnormal chondrocytic hypertrophy and subsequent failure of metaphyseal vascular penetration. The primary focus is on the osteochondroses, which currently are classified as over 50 different disease entities of the growth plate, named by anatomical location. Using morphological criteria from video-enhanced rectified interference contrast microscopy of living organ cultures, vital dye binding and lectin binding of living chondrocytes in situ, improved chemical fixation for light and selectron microscopy, and stereology, the three specific aims of the current proposal are: 1. To test the hypothesis that the process of cellular hypertrophy is controlled at three critical transition points. It is hypothesized that the hypertrophic cell zone does not consist of a continuum of cellular maturation in which each cell can be uniquely defined, but rather that the hypertrophic cell zone has three distinct subzones characterized by definable maturational stages. 2. To test the hypothesis that hypertrophic cell volume correlates positively with the of growth of a given growth plate. This hypothesis will be tested by using computerized serial section reconstructions and newly developed stereological techniques on a series of growth plates from multiple species, growing at different rates. 3, To test the hypothesis that hypertrophic cell volume is influenced by externally mediated perturbations which are known to alter the rate of long bone growth. The model will be the spontaneous correction of experimentally induced angular limb deformities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035155-08
Application #
3157062
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1985-07-01
Project End
1994-02-28
Budget Start
1992-07-01
Budget End
1994-02-28
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
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
Grover, Joel P; Vanderby, Ray; Leiferman, Ellen M et al. (2007) Mechanical behavior of the lamb growth plate in response to asymmetrical loading: a model for Blount disease. J Pediatr Orthop 27:485-92
Noonan, Kenneth J; Farnum, Cornelia E; Leiferman, Ellen M et al. (2004) Growing pains: are they due to increased growth during recumbency as documented in a lamb model? J Pediatr Orthop 24:726-31
Farnum, Cornelia E; Lee, Andrea O; O'Hara, Kathleen et al. (2003) Effect of short-term fasting on bone elongation rates: an analysis of catch-up growth in young male rats. Pediatr Res 53:33-41
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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