AJP - Endocrinology and Metabolism, Vol 238, Issue 3 200-E207, Copyright © 1980 by American Physiological Society
Influence of experimental diabetes and insulin on matrix-induced cartilage and bone differentiation
R. E. Weiss and A. H. Reddi
The influence of streptozotocin-induced diabetes on discrete stages of
matrix-induced endochondral bone formation has been investigated.
Mesenchymal cell proliferation was inhibited in diabetic rats as evidenced
by a 65% reduction of ornithine decarboxylase (ODC) activity and a 56%
reduction of [3H]thymidine incorporation per microgram DNA compared to
nondiabetic controls; the inhibition was prevented by insulin treatment. In
diabetic animals, chondrogenesis on day 7 was reduced by 49% compared to
control animals as assessed by 35SO4 incorporation. Exogenous insulin was
stimulatory to cartilage development when present during days 0 through 4
(mesenchymal cell proliferation). Calcification of cartilage and
osteogenesis were reduced by more than 50% in diabetic rats and corrected
by insulin as measured by alkaline phosphatase activity and 45Ca
incorporation. Decreased in vivo endochondral bone growth and development
during diabetes is the result of 1) inhibition of insulin-dependent
mesenchymal cell proliferation, 2) decreased and delayed cartilage
formation due to impaired mesenchymal cell proliferation, 3) decreased and
delayed vascular invasion prior to chondrolysis and osteogenesis, and 4)
reduced insulin-dependent calcification and ossification.
