Expression of cartilage-derived retinoic acid-sensitive protein during healing of the rat tooth-extraction socket

Cartilage-derived retinoic acid sensitive protein (CD-RAP) is a recently described, cartilage-specific protein. During early healing of the tooth-extraction socket, cells express both chondrogenic and osteogenic cell markers, but no cartilage is formed. Cartilaginous collagen type II protein, a major constituent of hyaline cartilage, has not been detected in the healing socket, although type IX collagen, which coats these fibres, has been detected transiently in early socket healing. This study investigated the spatial and temporal expression of CD-RAP and various osteoblast cell markers, i.e., alkaline phosphatase, osteopontin, osteonectin and osteocalcin, during healing. Immunolocalization of these proteins was determined in the rat tooth socket at 3, 4, 5, 6, 7, 8, 10 and 14 days after extraction. CD-RAP was expressed by preosteoblast cells maximally at 6, 7, and 8 days after extraction. Fully differentiated osteoblasts expressed osteocalcin, a specific osteoblast marker. Preosteoblasts and fibroblasts did not express osteocalcin. On double immunofluorescent staining, some preosteoblasts coexpressed CD-RAP (indicative of chondrogenic differentiation), and either alkaline phosphatase or osteopontin (markers of osteogenic stem-cell maturation). There was no colocalization between osteopontin and osteonectin. CD-RAP was unique amongst the cell markers used in that it was expressed by preosteoblasts, but not by osteoblasts lining the newly formed trabeculae. CD-RAP may have an important role in osteoblast cell differentiation during bone healing.