Lysosomes and Cartilage Resorption in Organ Culture 



55 





Indirect evidence for the role of lysosomes in skeletal morphogenesis is provided 

 by the work of Moscona and Karnofsky (1959). Administration of cortisone to the 

 chick embryo, in ovo, prevented the formation of the marrow cavity. In some species 

 cortisone produces mcreased 

 thickness of the epiphyseal plate 

 due to failure of resorption on 

 the metaphyseal side (Hulth 

 and Olerud, 1963). Both of 

 these findings I would interpret 

 as due to the stabilizing effect 

 of cortisone on the membranes 

 of cartilage lysosomes exposed 

 to the relative hyperoxia of a 

 highly vascularized region. 



In conclusion, it is suggested 

 that exposure of cartilage to 

 elevated partial pressures of 

 oxygen results in tissue degra- 

 dation by enzymes released by 

 lipid peroxidation of the lyso- 

 somal membrane. The often ob- 

 served association between vas- 

 cular invasion and degradation 

 of skeletal tissues and suscep- 

 tibility of cartilage to necrosis 

 in hyperoxia may therefore be 

 related. I would suggest that 

 this phenomenon has important 

 physiological as well as patho- 

 logical implications. Cases in point would be the increased vascularity of the 

 resorbing epiphyseal plate, the formation of the marrow cavity, the shedding of 

 decidious teeth in humans and antlers in deer, and the erosion caused by the vascular 

 pannus in rheumatoid arthritis. 



,^^ 



■^^?ii- 



8-day rudiment 



r 6 days. Osteo( 



cavitv formati 



on natural medium, exposed to S5"/o oxy- 

 lasts can be seen participating in marrow 

 >n. Haematoxvlin and Eosin. ■ 110 



Acknowledgements 



The author is a Fellow of The Medical Foundation Inc. of Boston, Massachusetts. 



I thank Dame Honor B. Fell, F. R. S. and Mr. J. T. Dingle for their interest 

 and advice. Certain aspects of this work were investigated in collaboration with 

 Mr. Dingle. 



References 



Ali, S. Y.: The degradation of cartilage matrix by an intracellular protease. Biochem. J. 93, 

 611 (1964). 



Allison, A. C: Role of lysosomes in oxygen toxicity. Nature (Lond.) 205, 141 (1965). 



Bassett, C. a. L.: Environmental and cellular factors regulating osteogenesis. In Bone Bio- 

 dynamics. Frost, H. M. (ed.). Boston: Little, Brown 1964, p. 233. 



— , and I. Herrmann: Influence of oxygen concentration and mechanical factors on differen- 

 tiation of connective tissues in vitro. Nature, (Lond.) 190, 460 (1961). 



