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Parathyroid hormone‐related peptide (PTHrP) and insulin‐like growth factor I (IGF‐I) are both involved in the regulation of bone and cartilage metabolisms and their interaction has been reported in osteoblasts. To investigate the interaction of PTHrP and IGF‐I during fracture healing, the expression of mRNA for PTHrP and IGF‐I, and receptors for PTH/PTHrP and IGF were examined during rat femoral fracture healing using an in situ hybridization method and an immunohistochemistry method, respectively. During intramembranous ossification, PTHrP mRNA, IGF‐I mRNA and IGF receptors were detected in preosteoblasts, differentiated osteoblasts and osteocytes in the newly formed trabecular bone. PTH/PTHrP receptors were markedly detected in osteoblasts and osteocytes, but only barely so in preosteoblasts. During cartilaginous callus formation, PTHrP mRNA was expressed by mesenchymal cells and proliferating chondrocytes. PTH/PTHrP receptors were detected in proliferating chondrocytes and early hypertrophic chondrocytes. IGF‐I mRNA and IGF receptor were co‐expressed by mesenchymal cells, proliferating chondrocytes, and early hypertrophic chondrocytes. At the endochondral ossification front, osteoblasts were positive for PTHrP and IGF‐I mRNA as well as their receptors. These results suggest that IGF‐I is involved in cell proliferation or differentiation in mesenchymal cells, periosteal cells, osteoblasts and chondrocytes in an autocrine and/or paracrine fashion. Furthermore, PTHrP may be involved in primary callus formation presumably co‐operating with IGF‐I in osteoblasts and osteocytes, and by regulating chondrocyte differentiation in endochondral ossification. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Journal of Orthopaedic Research – Wiley
Published: May 1, 2003
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