Impaired bone activity in aged rats: Alterations at the cellular and molecular levels

• Published in: Bone (New York, N.Y.) Vol. 13; no. 6; pp. 435 - 441
• Main Authors: Liang, C.T., Barnes, J., Seedor, J.G., Quartuccio, H.A., Bolander, M., Jeffrey, J.J., Rodan, G.A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 1992; Elsevier Science
• Subjects: Aging; Aging - physiology; Alkaline phosphatase; Alkaline Phosphatase - analysis; Animals; Biological and medical sciences; Bone Development - physiology; Bone induction; Bone Marrow; Collagen; Fundamental and applied biological sciences. Psychology; Gene Expression; Male; Marrow ablation; Models, Biological; Osteocalcin; Osteocalcin - analysis; Osteogenesis; Osteopontin; Procollagen - analysis; Rats; Rats, Wistar; RNA, Messenger - analysis; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Alkaline phosphatase; Osteocalcin; Collagen; Bone induction; Osteopontin; Aging; Marrow ablation; Senescence; Rat; Rodentia; Exploration; Experimental study; Gene expression; Northern blotting; Pathology; Vertebrata; Mammalia; Bone mass; Messenger RNA; Gene; Mineralization; Animal; Osteoblast; Skeleton; Molecular biology
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/8756-3282(92)90087-D

We have used a model of rapid bone induction and resorption in rats initiated by the removal of bone marrow to define age-associated deficits. Here we report the sequential expression of various genes implicated in the formation and removal of bone following marrow ablation. Significant increases in alkaline phosphatase and procollagen α 1(I) mRNA were observed by day 5, and of osteocalcin and osteopontin by day 6. At their peak, these mRNA levels were elevated three- to eight-fold and correlated with histological evidence of bone formation. No change in collagen II mRNA was observed, indicating that there was no cartilage phase. Collagenase activity increased 10-fold at day 9 and coincided with the beginning of bone resorption. Actin mRNA, a reference gene marker, remained at constant levels. Comparison of the response between adult (6 mo.) and old (24 mo.) rats showed the same temporal pattern, but a lower expression of bonerelated genes in older rats. Histological examination also showed that the bone volume and osteoblast number at day 6 were significantly lower in old rats. Furthermore, the percentage of mineralized bone was greatly reduced in the aged rat. This model system is currently being used to evaluate the effectiveness of interventions to up-regulate the bone activity in senescent rats.