TEMPORAL EXPRESSION OF PTHRP DURING ENDOCHONDRAL BONE-FORMATION IN MOUSE AND INTRAMEMBRANOUS BONE-FORMATION IN AN IN-VIVO RABBIT MODEL

Expression of parathyroid hormone-related protein (PTHrP) messenger RN A (mRNA) and protein was investigated throughout the developmental pro gression of endochondral bone formation in mouse and intramembranous b one formation in an in vivo model in rabbit, using in situ hybridizati on and immunohistochemistry. Endochondral bone formation was investiga ted in a developing embryo, newborn, and adult mouse. In fetal long bo nes through to newborn (day 7), PTHrP mRNA and protein were consistent ly expressed in chondrocytes within the proliferative, transitional, a nd hypertrophic zones. In addition, high levels of PTHrP were also det ected in osteoblasts on the surface of trabecular bone surfaces. Simil arly, at the adult stage (week 7), PTHrP mRNA and protein were consist ently expressed in chondrocytes at epiphyseal ends of the subarticular cartilage, within cortical periosteum, as well as in osteoblasts loca ted at the metaphyseal trabecular bone surfaces. Using an in vivo intr amembranous bone formation model in rabbits, expression of PTHrP mRNA and protein was demonstrated in preosteoblasts prior to trabecular bon e formation (1-week bone harvest). As bone formed (2-, 3-, and 4-week bone tissue harvests), PTHrP mRNA and protein were highly expressed in actively synthesizing osteoblasts and in those osteocytes embedded wi thin the superficial layers of the bone matrix. Lining osteoblasts and osteocytes buried deeply in the bone matrix displayed weak or no sign al for PTHrP. The pattern of spatial and temporal expression of PTHrP demonstrated in cartilage cells and osteoblasts in the two systems sug gests an important role of PTHrP in both endochondral and intramembran ous bone formation. (C) 1997 by Elsevier Science Inc. All rights reser ved.