Chondrocyte apoptosis enhanced at the growth plate: a physeal response to a diaphyseal fracture

Abstract

Post-traumatic overgrowth of growing long bones is a common clinical phenomenon in paediatric traumatology and is the result of an enhanced stimulation of the nearby growth plate after fracture. To date, the exact post-fractural reactions of the growth plate are poorly understood. The aim of this study has been to determine the impact of fracture on the frequency of chondrocyte apoptosis of the growth plate. Rats sustained a mid-diaphyseal closed fracture of the left tibia or were left untreated. All animals were killed 3, 10, 14 or 29 days after trauma. The left and right tibiae were harvested and apoptotic chondrocytes of the proximal tibial growth plate were detected by TUNEL staining. The apoptosis percentage of physeal chondrocytes was statistically compared among fractured bones, intact contra-lateral bones and control bones. The physeal apoptosis rate of the fractured bone was significantly higher than that of the contra-lateral intact bone (valid for all evaluated days) and the control bone (valid from day 10 onwards). Contra-lateral intact tibiae never showed significantly higher apoptosis rates compared with control tibiae. Thus, mid-diaphyseal fracture influences the nearby growth plate by stimulating chondrocyte programmed cell death, which is associated with cartilage resorption and bone replacement. The lack of a significant difference between the intact contra-lateral and the intact control bone suggests that fracture only has a local effect that contributes to the greater apoptosis rate of the adjacent physis.

Post-Traumatic Caspase-3 Expression in the Adjacent Areas of Growth Plate Injury Site: A Morphological Study

“…Morphological analysis of our study supports literature data [2,4,6,7,14–18]. When the bone bridge is large enough, the defect will result in some growth arrest, leading to angular deformities or longitudinal shortening [8].…”

“…These data were also strengthened by Western Blot analysis, in vitro , where caspase-3 and cleaved PARP-1 expression significantly increased in growth plate chondrocytes with a time-course progression in experimental rats. Although we used apoptotic markers, such as caspase-3 and cleaved PARP-1, different from those used by other researchers, our study supports data from literature [2,7]. In the current study, we also investigated the expression of IL-6 and TNF-α serum levels within 24 h after growth plate damage, coinciding with the initial acute transient inflammatory phase, which was accompanied by a large influx of immune cells to the injury site.…”

“…The growth plate has a very specific zonal arrangement, including a relatively inactive reserve zone at the epiphyseal end, moving distally into a proliferative and then hypertrophic zone and ending with a band of ossifying cartilage (the metaphysis). A mnemonic for remembering the names of the epiphyseal growth plate zones is: Resting zone, Proliferative zone, Hypertrophic cartilage zone, Calcified cartilage zone, Ossification zone [2,3]. The growth plate is clinically relevant in that, before growth is complete, the physis is susceptible to fractures because it is the most fragile region of the long bones and is prone to trauma injury.…”

Osteoporosis increases chondrocyte proliferation without a change in apoptosis during fracture healing in an ovariectomized rat model

“…Our study found that chondrocyte apoptosis occurred during the entire period of fracture healing; this finding is consistent with previous findings (18). Chondrocyte apoptosis increased during the process of fracture healing, reaching a peak on day 20 post-fracture, at which point the proliferation of chondrocytes was in decline, Numerous typical hypertrophic chondrocytes were observed in cartilage tissue, suggesting that apoptosis enhanced the maturation of cartilage tissue and endochondral ossification (19). In the present study, no significant difference in chondrocyte apoptosis was noted between the sx and ovx rats.…”

Electrical Implications of Corrosion for Osseointegration of Titanium Implants

“…In children, fractured long bones tend to overgrow with respect to their counterparts (Aitken et al, 1939;Wray and Goodman, 1961), and there is an increase in apoptosis in the growth plate (Gaber et al, 2009). Interestingly, both the healing site and growth plate tend to have a more negative potential compared with that of the nearby intact tissue (Friedenberg and Brighton, 1966;Black, 1986) (Fig.…”