Growth parameters in the epiphyseal cartilage of brachymorphic (bm/bm) mice

We studied kinetics in the epiphyseal cartilage of the brachymorphic (bm/bm) mouse, combining morphometry and labeling with halogenated nucleotides. The defective synthesis of the sulfate donor PAPS in these homozygous mutants is evident in tissues with a large production of glycosaminoglycans; these compounds become undersulfated. Compared with their heterozygous siblings, the longitudinal growth of the mutant mice was reduced by two-thirds. This was mainly associated with (1) reduced height of the proliferating zone, (2) a substantial number of G0 cells in this zone, and (3) reduced hypertrophy which, in turn, may be related to premature mineralization and prevention of normal expansion of cells. No significant effects on cell-cycle parameters were detected, such as S-phase time or cell-cycle time, and the rate at which each cell increased the matrix volume seemed normal. An effect on matrix mineralization may be related to known changes in the structure of matrix PGs, whereas the effect on proliferation may be related to other factors. Candidates for such other effects of undersulfation are the cell surface PGs, which are important for binding of growth factors.