IMPAIRED EXPRESSION OF NONCOLLAGENOUS BONE-MATRIX PROTEIN MESSENGER-RNAS DURING FRACTURE-HEALING IN ASCORBIC ACID-DEFICIENT RATS

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis, To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and c hondrogenic cells, we examined the expression of genes encoding bone m atrix proteins, including osteonectin (ON), osteopontin (OPN), osteoca lcin (OC), and matrix Gla protein (MGP), as differentiation markers fo r osteogenic and chondrogenic cells during fracture healing in Osteoge nic Disorder Shionogi (ODS) rats, which have a hereditary defect in th e ability to synthesize ascorbic acid (Asc), In ODS rats without Asc s upplementation, intramembranous ossification was completely inhibited, Although a few fibroblast-like cells expressing ON mRNA were observed , no OPN mRNA-expressing cells were detected, During endochondral ossi fication, a small amount of metachromatic staining cartilage appeared at the fracture site, but there,vas no provisional calcification zone in the cartilage, Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA, When Asc was given to these rats, callus formation was soon det ected around the fracture site, while OPN mRNA was expressed by differ entiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the i ncrease of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells, Since OPN is considered to play an impor tant role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.