The growth plate: a physiologic overview

Abstract

The growth plate is the cartilaginous portion of long bones where the longitudinal growth of the bone takes place. Its structure comprises chondrocytes suspended in a collagen matrix that go through several stages of maturation until they finally die, and are replaced by osteoblasts, osteoclasts, and lamellar bone.The process of endochondral ossification is coordinated by chondrocytes and a variety of humoral factors including growth hormone, parathyroid hormone, oestrogen, growth factors, cytokines, and various signalling pathways.Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.The highly complex regulatory signals involved in this process are genetically determined, and genetic perturbations in any of the associated genes can result in abnormalities of bone growth. Hundreds of chondrodysplasias have been described, pointing to the complexity of the humoral control systems involved in endochondral ossification.While our knowledge of the mechanisms behind the various bone growth control systems is improving, a deeper understanding of the underlying processes could aid clinicians to better understand bone health and bone growth abnormalities. This review describes the current clinical research into the physiology of the growth plate. Cite this article: EFORT Open Rev 2020;5:498-507. DOI: 10.1302/2058-5241.5.190088.

Keywords: bone growth; chondrodysplasia; growth plate; physis.

Fig. 1

Zones of chondrocyte maturation in growth plate. Source. This figure is licensed under the Creative Commons Attribution-Share Alike 4.0 International license from Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, 19 June 2013.

Fig. 2

Paracrine control of growth plate. Notes. Ihh (Indian hedgehog) enhances the proliferation and maturation of chondrocytes and induces the expression of parathyroid hormone-related protein (PTHrP) in the periarticular region. PTHrP prevents premature hypertrophic differentiation. The negative feedback loop between Ihh and PTHrP keeps chondrocytes in the proliferating state, controls chondrocyte proliferation, and maintains the lengths of columns. Ihh and bone morphogenic protein (BMP) are in a positive feedback loop with each other and up-regulate chondrocyte proliferation together. In addition, BMP inhibits the development of terminally differentiated chondrocytes. Fibroblast growth factor (FGF) signalling is antagonistic to BMP activity. FGF expression down-regulates chondrocyte proliferation and hypertrophy by inhibiting Ihh and promotes chondrocyte differentiation. Runt-related transcription factor 2 (RUNX2) positively regulates Ihh expression and promotes chondrocyte proliferation, but it is inhibited by PTHrP, which is induced by Ihh. Sox-9 signalling contributes to chondrogenesis in different steps. Sox-9 up-regulates chondrogenic mesenchymal condensation, chondrocyte differentiation, and normal chondrocyte proliferation and inhibits the transition of proliferating chondrocytes to hypertrophy. Insulin-like growth factor 1 (IGF-1) signalling modulates chondrogenesis by both suppressing PTHrP production and inducing the mammalian target of rapamycin (mTOR) signalling activity, which plays a role in all stages of chondrocyte maturation.

Fig. 3

Components of the extracellular matrix (ECM). Source. This figure is is licensed under the Creative Commons Attribution-Share Alike 4.0 International license from Kassidy Veasaw.