Structural and molecular analyses of bone bridge formation within the growth plate injury site and cartilage degeneration at the adjacent uninjured area

• Published in: Bone (New York, N.Y.) Vol. 49; no. 4; pp. 904 - 912
• Main Authors: Macsai, C.E, Hopwood, B, Chung, R, Foster, B.K, Xian, C.J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.10.2011
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cartilage - metabolism; Cartilage - pathology; Cell Proliferation; Chondrocytes - metabolism; Chondrocytes - pathology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Growth Plate - metabolism; Growth Plate - pathology; Male; Orthopedics; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism; Salter-Harris Fractures; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Degeneration; Bone bridge; Proliferation; Chondrocytes; Apoptosis; Epiphyseal cartilage; Chondrocyte; Morphology; Bone
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2011.07.024

Abstract Injury to the growth plate is common and yet the injured cartilage is often repaired with undesirable bony tissue, leading to bone growth defects in children. Using a rat tibial growth plate injury model, our previous studies have shown sequential inflammatory, fibrogenic, osteogenic and bone maturation responses involved in the bony repair. However, it remains unclear whether there is progressive accumulation of bone within the injury site and any potential degenerative changes at the adjacent non-injured area of the growth plate. This study examined effects of growth plate injury on the structure, composition and some cellular and molecular changes at the injury site and adjacent uninjured area. Micro-CT analysis revealed that while the bone volume within the injury site at day 14 was small, the bone bridge was considerably larger at the injury site by 60 days post-injury. Interestingly, formation of bone bridges in the adjacent uninjured area was detected in 60% of injured animals at day 60. Immunohistochemical analyses revealed reduced chondrocyte proliferation (PCNA labelling) but increased apoptosis (nick translation labelling) in the adjacent uninjured area. RT-PCR analysis on adjacent uninjured growth plate tissue found increased expression of osteocalcin at day 60, differential expression of apoptosis-regulatory genes and alterations in genes associated with chondrocyte proliferation/differentiation, including Sox9 and IGF-I. Therefore, this study has demonstrated progressive changes in the structure/composition of the injury site and adjacent uninjured area and identified cellular and molecular alterations or degeneration in adjacent uninjured growth plate in response to injury.