Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics

Abstract

Differential elongation of growth plates is the process by which growth-plate chondrocytes translate the same sequence of gene regulation into the appropriate timing pattern for a given rate of elongation. While some of the parameters associated with differential growth are known, the purpose of this study was to test the hypothesis that eight independent variables are involved. We tested this hypothesis by considering four different growth plates in 28-day-old Long-Evans rats. Temporal parameters were provided by means of oxytetracycline and bromodeoxyuridine labeling techniques. Stereological parameters were measured with standard techniques. For all four growth plates, the calculated number of new chondrocytes produced per day approximated the number of chondrocytes lost per day at the chondro-osseous junction. This suggests that the proposed equations and associated variables represent a comprehensive set of variables defining differential growth. In absolute numbers, the proximal tibial growth plate produced about four times as many chondrocytes per day as the proximal radial growth plate (16,400 compared with 3,700). In the proximal tibia, 9% of growth is contributed by cellular division; 32%, by matrix synthesis throughout the growth plate; and 59%, by chondrocytic enlargement during hypertrophy. In the more slowly elongating growth plates, the relative contribution to elongation from cellular enlargement decreases from 59 to 44%, with a relative increase in contribution from matrix synthesis ranging from 32% in the proximal tibia 49% in the proximal radius. This study suggests that differential growth is best depicted as a complex interplay among cellular division, matrix synthesis, and cellular enlargement during hypertrophy. Differential growth is best explained by considering a set of eight independent variables, seven of which vary from growth plate to growth plate. Thus, this study confirms the importance of cellular hypertrophy during elongation and adds to our understanding of the importance of locally mediated regulatory systems controlling growth-plate activity.

Ontogeny of Skeletal Maturation in the Juvenile Rat

“…However, that we fail to see substantial BrdU uptake in the growth plate and that there are few remaining chondrocytes of either proliferative or hypertrophic morphology in the growth plate of these older animals (Fig. 6E) suggests that whatever growth accrues at these advanced ages is not likely a product of chondrocytic duplication and hypertrophic enlargement (Wilsman et al, 1996). Rather, it is possible and indeed quite likely that this residual elongation and may be the product of some interstitial growth mechanism such as matrix secretion (Pavasant et al, 1996), rather than the product of a persistent primary endochondral process.…”

Ossification of the mouse metatarsal: Differentiation and proliferation in the presence/absence of a defined growth plate

“…However, natural variation exists in the ossification and growth between individual physes, even within the same bone (Digby, 1915;Payton, 1932;Bisgard and Bisgard, 1935;Pritchett, 1991;Reno et al, 2000). Comparisons between growth plates of different ages or locations have improved our understanding of the physiological mechanisms specifying growth rate (Hunziker and Schenk, 1989;Wilsman et al, 1996aWilsman et al, , 1996b), yet the significant natural variation that exists during formation and growth of the normal mammalian skeleton continues to be an underutilized tool for understanding the regulation of growth plate formation. One striking example is the short tubular bones (metacarpals, metatarsals, and phalanges) of the hands and feet of humans.…”

Mechanics of chondrocyte hypertrophy

“…In simulations, additional tensions of 0.1, 0.05, −0.05 and −0.1 MPa are applied in the direction of growth, to enable comparison with experimental studies (Robling et al 2001;Stokes et al 2006Stokes et al , 2007. Ultimate chondrocyte height, representative for bone growth rate (Wilsman et al 1996), correlates with applied tension. Compression (8.2% reduction of cell height at −0.1 MPa loading) is predicted to be slightly less effective than tension (12.2% enhanced growth at +0.1 MPa loading) in modulating hypertrophy with the default parameter set.…”

“…The intracellular volumes occupied by organelles and cytoplasmic ground substance gradually increase (Buckwalter et al 1986), together with the osmotic pressure generated by intracellular accumulation of organic osmolites (Farnum et al 2002). Although quantification of the effects of cellular electro-chemo-mechanical properties has proven difficult, it is apparent that this can only be partially responsible for the tenfold volume change and four to five times increased cell height during hypertrophy (Buckwalter et al 1986;Hunziker and Schenk 1989;Noonan et al 1998;Wilsman et al 1996). Interestingly, to keep up with such increase in cell height, the aligning extracellular matrix (ECM) needs to also stretch to 400-500% its original length.…”

“…The combined effect of changes in cell volume and matrix constitution is that the volume occupied by cells over the volume of ECM decreases from the early proliferative to the late hypertrophic zone. Yet, the total amount of matrix associated with one hypertrophic cell increases, with values ranging from 50 to 1000% depending on species, age and growth plate (Buckwalter et al 1986;Farnum et al 2002;Hunziker and Schenk 1989;Wilsman et al 1996) (Fig. 1).…”