ALPHA-METHYL-PROLINE RESTORES NORMAL LEVELS OF BONE-COLLAGEN TYPE-I SYNTHESIS IN OVARIECTOMIZED RATS

Collagen type is the major protein of bone matrix and significantly re duced in osteoporosis. We tested the effect of alpha - methyl - prolin e on collagen synthesis in the model of the ovariectomized rat. Collag en synthesis was studied at the transcriptional level using Northern a nd dot blotting and at the protein level using hydroxyproline determin ation and a specific dye binding collagen assay. Alpha - methyl - prol ine treatment significantly increased collagen synthesis as compared t o untreated ovariectomized and estradiol treated ovariectomized rats a nd restored collagen synthesis to levels of sham operated rats. Prolin e analogues were described to stimulate procollagen synthesis at the t ranscriptional level, however, if incorporated, lead to negative colla gen production due to rapid intracellular degradation of the deficient collagen. Our synthesized analogue is not being incorporated, thus no t interfering with collagen conformation and can therefore induce coll agen production.