This theory is the most widely held hypothesis. Hypertrophic chondrocytes of the growth plate undergo death by apoptosis, leaving behind a frame of cartilage matrix for osteoblasts that invade and lay down bone. Some supporting and opposing results for this hypothesis have been reported in several studies 8.
Apoptosis-regulating proteins such as caspases were expressed in the growth plate and typical histologic changes in cell during apoptosis were shown in several studies in rat 9. However, another study found no signs of classical apoptosis in fusing human growth plates Autophagy is another method of programmed cell death that involves a catabolic process in which the cell degrades its own components through autophagosomes.
Signs of autophagy autophagosomes, double-membrane structures, and condensed chromatin were observed in avian hypertrophic chondrocytes and chondrocytes of newborn mice 11 , However, there were no autophagosomes or signs of autophagy in the growth plate in a study in humans 7.
Emons et al. They postulated that the dense border might act as a physical barrier preventing oxygen and nutrients from reaching the fusing growth plate, resulting in hypoxia and eventually cell death in a nonclassical apoptotic manner. Stewart et al. This is the oldest hypothesis, in which terminal hypertrophic chondrocytes transdifferentiate into osteoblasts at the chondroosseous junction of the growth plate This theory is mostly based on organ and cell culture models and there is a lack of direct evidence in human studies 7.
The conversion of progenitor cells in the mesenchymal condensation into chondrocyte lineage is controlled by the expression of the transcription factors Sox9, 5, and 6 8. Parathyroid hormone-related peptide PTHrP signaling, Indian hedgehog IHH pathway, and runt-related transcription factor 2 Runx2 are required for further differentiation and hypertrophy of chondrocytes. In addition to those factors, fibroblast growth factor FGF pathway and bone morphogenic proteins BMP are necessary for the development of the perichondrium, periosteum, chondrocytes, and osteoblasts 7 , Of these paracrine factors, the best studied one is PTHrP that is known as secreted by periarticular chondrocytes of long bones 16 , 17 , Hirai et al.
And it also has independent effects on chondrocyte differentiation BMP signaling across the growth plate is considered to contribute to the progressive differentiation of resting to proliferative to hypertrophic chondrocytes 20 , 21 , Vascular invasion is a prerequisite for the replacement of avascular cartilage by vascular bone and marrow. The most important stimulating factor for vessel invasion is hypoxia.
Vessel formation is mediated by transcription factors, including hypoxia-inducible factor-1 and vascular endothelial growth factor VEGF 25 , There are five steps in differentiation of the osteoblastic lineage. These steps are the preosteoblast, mature osteoblast, osteoid osteocyte, early osteocyte, and mature osteocyte During these steps, bone can deposit minerals from the extracellular matrix rich in type I collagen, completing ossification 4.
They are also important for the acquisition of bone mass during the prepubertal period and maintenance of bone homeostasis throughout life. For differentiation, proliferation, and hypertrophy of chondrocytes; the production of extracellular matrix; and ossification in the growth plate, IGF-I produced from chondrocytes of the epiphyseal plate is important There is a close interplay between estrogen and GH in the regulation of growth and development in puberty.
During puberty, there can be a 1. However, the interactions between estrogen and GH at the growth plate remain unclear because there is a lack of evidence of the independent roles of these two hormones at the cellular level in the growth plate 30 , In the classical pathway, estrogen acts after binding with its receptor estrogen receptor, ER.
Both subtypes seem to be involved in the augmentation of GH secretion and are expressed in the resting, proliferative, and hypertrophic zones of the growth plate. Indirect evidence suggests that epiphyseal fusion occurs when the proliferative capacity of growth plate chondrocytes is exhausted and estrogen acts by advancing growth plate senescence.
Therefore, the binding of estrogen with each subtype of ER is thought to be related to the pubertal growth spurt and epiphyseal fusion 32 , 33 , 34 , Borjesson et al. They suspected that activation of the GH-IGF-I axis with low doses of estrogen is important for the pubertal growth spurt in early puberty, while high doses of estrogen binding to its receptors in growth plate cartilage are essential for epiphyseal fusion in late puberty.
The effects of estrogen on the growth plate have been studied in many rodent models. However, there are some differences in growth plate physiology between rodents and humans.
In rats or mice, the pubertal growth spurt is unremarkable and longitudinal bone growth continues even after sexual maturation, as epiphyseal fusion does not occur at the time of sexual maturation. Therefore, there are difficulties in the direct application of growth plate studies in rodents to humans 5.
Further molecular studies are needed to elucidate the consequences of estrogen and the ER in growth plates. Estrogen is known to promote bone formation by stimulating osteoblastogenesis and inhibiting apoptosis of mature osteoblasts.
Androgen itself also contributes to bone formation and the pubertal growth spurt, perhaps through a direct interaction with growth plate chondrocytes Dihydrotestosterone can stimulate proliferation and proteoglycan synthesis in growth plate chondrocytes in vitro and testosterone stimulates chondrocyte proliferation in an organ culture model study with increased local IGF-I production 5.
Overview Growth plate fracture Open pop-up dialog box Close. Growth plate fracture Growth plates are located near the ends of your child's bones. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Growth plate injuries. Accessed March 29, Growth plate fractures.
American Academy of Orthopaedic Surgeons. Mathison DJ, et al. General principles of fracture management: Fracture patterns and description in children. This happens in girls around ages 13—15 and in boys around ages 15— A growth plate fracture is a break in the growth plate of a child or teen. They happen most often in the bones of the fingers, forearm, and lower leg. Most growth plate fractures happen from falling or twisting.
Contact sports like football or basketball or fast-moving activities like skiing, skateboarding, sledding, or biking are common causes. Growth plate fractures also can happen from repetitive activities, like training for gymnastics or pitching a baseball. A child with a growth plate fracture can have pain, swelling, and trouble moving and using the injured body part. Sometimes there is a deformity — this means that the body part looks crooked or different than it did before the injury.
Health care providers will order X-rays if they think a bone is broken. Related Articles. Childhood Injuries: Sprain vs. Trending Topics. What Parents Need to Know. What You Should Know About Growth Plate Injuries Growth plates, thin cartilage discs at the end of long bones in children, can get injured just like bones.
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