The Growth Plate: Embryologic Origin, Structure, and Function

Introduction

Skeletal formation and growth occur as a process of sequential morphologic and biochemical events that take place during fetal development. During development, bone tissue is formed and grows through one of two processes. Bone can form directly from mesenchymal tissue, which is called intramembranous ossification. This occurs at the periosteal surfaces of all bones and in parts of the pelvis, scapula, clavicles, and skull. Alternatively, bone tissue can form by replacement of a cartilaginous model, which is referred to as endochondral ossification. Endochondral ossification occurs at the base of the skull, the vertebrae, and at the growth plates of the appendicular skeleton.

Proliferating cartilage constitutes the basis for much of the size increase of bones as organs, because bone tissue itself does not grow interstitially. In the long bones of the limbs the proliferating cartilage is located at the ends, in the form of what is known as a growth plate, physeal plate, or physis. The cartilage in the growth plate has a unique zonal structure, biochemistry, process of matrix mineralization, and blood supply that differs markedly from hyaline or articular cartilage. Other areas of the body that have proliferating cartilage of various configurations include the skull (sutures and the base), the spine (end plates and synchondroses), the pelvis (triradiate cartilages), and the carpus and tarsus.

Development of the Growth Plate

Limb development has been studied in various organisms. Chick studies provided a wealth of information in the past because of the accessibility of the limb bud in ovo. However, molecular studies have focused largely on the mouse embryo. Cross-species transplants have indicated that many of the same signals control limb formation in both organisms. Additional information about limb patterning has been derived from the study of regenerating amphibian limbs.

The formation of the developing limb bud in vertebrates is initiated by the mesenchyme. Somites give rise to all limb muscle cells, whereas the lateral plate mesoderm gives rise to connective tissue and cartilage and thus determines the primary limb pattern. ^, In the absence of somites, the lateral plate mesoderm forms a limb with normal skeletal structure and tendons, which is devoid of any musculature.

The embryonic limb bud formation is initiated during the fourth week of gestation by the lateral plate mesoderm as a small projection on the ventrolateral body wall. This mesenchymal projection is covered by ectoderm, the tip of which thickens and becomes what is known as the apical ectodermal ridge (AER) ( Fig. 137.1 ), which drives limb outgrowth and proximodistal patterning. Underlying the AER are rapidly proliferating, undifferentiated mesenchymal cells that form what is known as the progress zone (PZ). Proliferation of these cells causes limb outgrowth. The events in upper and lower limb buds are similar in character and sequence. However, a slight craniocaudal time gradient exists, with the upper limb bud appearing and progressing 1 to 2 days before the lower limb bud. The molecular interaction between the AER and the underlying undifferentiated mesenchymal cells (PZ) drives limb development. Once the process of differentiation of all limb elements is complete, the AER disappears. Clinically, limb bud development is first identifiable by transvaginal ultrasound at 8 weeks.

As the limb bud grows, three major limb axes appear at different times and by different mechanisms ( Fig. 137.2 ). The limb bud develops asymmetries along the proximodistal (flank to digit tip), anteroposterior (thumb to small finger), and dorsoventral (back of hand to palm) axes. Some of the important signals for initiating and maintaining these axes have been described in literature and will be discussed later in this chapter. The genes that initiate and potentiate signals in different axes often interact and are regulated via feedback mechanisms, resulting in effects in multiple planes of growth.