Genetic Regulation of the Growth Plate

Abstract

The epiphyseal growth plate consists of a layer of cartilage present only during the growth period and vanishes soon after puberty in long bones. It is divided to three well-defined zones, from epiphyses; resting, proliferative, and hypertrophic zones. Chondrocyte proliferation and differentiation and subsequent bone formation in this cartilage are controlled by various endocrine, autocrine, and paracrine factors which finally results into elimination of the cartilaginous tissue and promotion of the epiphyseal fusion. As chondrocytes differentiate from round, quiescent, and single structure to flatten and proliferative and then large and terminally differentiated, they experience changes in their gene expression pattern which allow them to transform from cartilaginous tissue to bone. This review summarizes the literature in this area and shortly describes different factors that affect growth plate cartilage both at the local and systemic levels. This may eventually help us to develop new treatment strategies of different growth disorders.

Pubertal growth and epiphyseal fusion

“…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 , 15) .…”

Current Knowledge on Exostoses Formation in Hereditary Multiple Exostoses: Where do Exostoses Originate and in What Way is their Growth Regulated

“…At the end of puberty, the width of the epiphysis decreases and eventually the epiphysis is completely closed and replaced by bone. This process is controlled by various endocrine, autocrine, and paracrine factors [70].…”

“…In a later stage the BMP proteins are expressed in the perichondrium as well as hypertrophic and proliferative chondrocytes. Indian hedgehog expression in prehypertrophic chondrocytes increases through BMP signaling thereby increasing both the rate of chondrocyte proliferation and the length of proliferative columns [70,88]. Since HS and HSPG act as co-receptors for BMP's in HME patient we expect therefore a decrease in the rate of chondrocyte proliferation and a shorting of the proliferative columns, which may lead to shortage or axial deviation (in case of partial decreased growth rate) of the long bones.…”

“…The expression of FGFs and their receptors in postnatal growth plate cartilage suggests that these proteins contribute to growth plate senescence and thus help to determine the size of the adult skeleton [70,89].…”

The effect of electric fields on hyaline cartilage: an in vitro and in silico study

“…[16], [21], [27]. The correct expression of Ihh and PTHrP are related with a normal growth of long bones; nevertheless, a disruption in the secretion of one of these molecules can result in pathologies such as acrocapitofemoral dysplasia, which is associated with premature closure of the growth plates, Blomstrand dysplasia, which may cause death in the uterus due to an advanced endochondral maturation, and short stature due to a delay in hypertrophic chondrocyte differentiation [132]. Several studies have demonstrated that a mutation of PTHrP or Ihh leads to a decrease in trabecular bone formation in the POC and a delay in angiogenesis of the early cartilage model [133], alterations in the temporal and spatial sequence of epiphyseal cartilage development [134], reduction in the size of the growth plates of long bones [135], and shortness of absent middle phalanges in digits [136].…”