Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats.

Abstract

SUMMARY1. Chondrocyte activities within growth plate cartilage are the principal determinants of longitudinal bone growth, and it was the aim of this investigation to assess how these cell activities are modulated under various growth rate conditions.Using proximal tibial growth plates from rats of different ages, growth rate was determined by fluorochrome labelling and incident light fluorescence microscopy. Various cellular parameters contributing to longitudinal bone growth were quantified by light microscopic stereology. The size of the proliferating cell population ('growth fraction') was estimated by autoradiography (using [3H]thymidine labelling).2. A comparison between data for suckling (21-day-old) and fast-growing (35-dayold) rats revealed that growth acceleration is achieved almost exclusively by cellshape modelling, namely by an increase in final cell height and a decrease in lateral diameter, whereas final cell volume and surface area are slightly reduced. Cell proliferation rate in the longitudinal direction and net matrix production per cell remain unchanged. The physiological increase in linear growth rate thus appears to be based principally upon a controlled structural modulation of the chondrocyte phenotype. On the other hand, a physiological reduction in growth rate (i.e. growth deceleration) effected during the transition from pre-puberty (35-day-old rats) to maturity (80-day-old rats) is achieved by simultaneous decreases in several chondrocyte parameters, including cell height (i.e. phenotype modulation), cell volume and proliferation rate (in the longitudinal direction

Mechanics of chondrocyte hypertrophy

“…Unfortunately, this difference between ITM and PCM cannot be verified with experimental data. Another study documented that a chondrocyte with tenfold increased volume will have gained four times its original cell height (Hunziker and Schenk 1989), which is in agreement with the prediction that a cell that volume reaches 3.6-fold the original cell height.…”

“…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).…”

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

“…Thus, the proliferative reserve zone may play a central role in preventing the primary center of ossification from encroaching on the epiphysis, thus allowing maintenance of the growth plate. Traditionally, reserve zone chondrocytes are defined in established growth plates by cells that occur individually or in pairs with random orientation to the longitudinal axis of the bone (Hunziker and Schenk, 1989). As yet, no cellular marker has been conclusively demonstrated to be specific to reserve chondrocytes.…”

“…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.…”