Aberrant metabolism of matrix components in neonatal fibular cartilage of brachypod (bp H) mice

Abstract

Collagen and the acid mucopolysaccharides (AMPS) were studied in the fibular cartilage of brachypod ( bp H bp H ) and normal (+/+) newborn mice. At this age the mutant fibulae are still cartilaginous and are comprised of closely packed chondrocytes, homogenous in size and shape. Brachypod fibular chondrocytes synthesized a normal cartilage-type collagen molecule but at half the normal rate. Incorporation of tryptophan indicated this was related to a depression of general protein synthesis rather than being specific for collagen. Pulse-chase experiments showed that collagen degradation over a 3-day culture period was 15% slower than normal thus accounting for the higher collagen content in mutant fibulae. AMPS synthesis in normals and brachypods was nearly equal; however, in pulse-chase experiments radioactivity could not be chased out of the mutant tissue. The failure of AMPS degradation also accounted for greater than normal quantity of AMPS in the mutant cartilage. Characterization of the AMPS led to the discovery of a small population of unsulfated chondroitin molecules in normal, but not brachypod cartilage. The importance of a coordinated metabolism of matrix products during limb development is discussed.