Growth plate mechanics and mechanobiology. A survey of present understanding

Abstract

The longitudinal growth of long bones occurs in growth plates where chondrocytes synthesize cartilage that is subsequently ossified. Altered growth and subsequent deformity resulting from abnormal mechanical loading is often referred to as mechanical modulation of bone growth. This phenomenon has key implications in the progression of infant and juvenile musculoskeletal deformities, such as adolescent idiopathic scoliosis, hyperkyphosis, genus varus/valgus, tibia vara/ valga, as well as neuromuscular diseases and clinical management of these deformities is often directed at modifying the mechanical environment of affected bones. However, there is limited quantitative and physiological understanding of how bone growth is regulated in response to mechanical loading. This review of published work addresses the state of knowledge concerning key questions about the mechanisms underlying biomechanical modulation of bone growth. The longitudinal growth of bones is apparently controlled by modifying the numbers of growth plate chondrocytes in the proliferative zone, their rate of proliferation, the amount of chondrocytic hypertrophy and the controlled synthesis and degradation of matrix throughout the growth plate. These variables may be modulated to produce a change in growth rate in the presence of sustained or cyclic mechanical load. Tissue and cellular deformations involved in the transduction of mechanical stimuli depend on the growth plate tissue material properties that are highly anisotropic, time-dependent, and that differ in different zones of the growth plate and with developmental stages. There is little information about the effects of time-varying changes in volume, water content, osmolarity of matrix, etc. on differentiation, maturation and metabolic activity of chondrocytes. Also, the effects of shear forces and torsion on the growth plate are incompletely characterized. Future work on growth plate mechanobiology should distinguish between changes in the regulation of bone growth resulting from different processes such as direct stimulation of the cell nuclei, physicochemical stimuli, mechanical degradation of matrix or cellular components and possible alterations of local blood supply.Address for notification, correspondence and reprints: Isabelle Villemure, P.Eng., Ph.D., Department of Mechanical Engineering, Ecole Polytechnique of Montreal, P.O. Box 6079, Station "Centre-Ville", Montréal, Québec, H3C 3A7, CANADA, Phone: 1 (514) 340-4711 ext. 4900, Fax: 1 (514) 340-4176, E-mail: isabelle.villemure@polymtl.ca. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertai...

Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants

“…Starting at the epiphyseal end of the growth plate, the flat and small chondrocytes (reserve zone) activate and start to proliferate (proliferative zone), thereafter growing in size (hypertrophic zone) toward the metaphysic, ultimately resulting in chondrocyte apoptosis, blood vessel invasion into the extracellular matrix, and finally ossification into bone tissue. (8,9) We hypothesized that markers reflecting cartilage or bone metabolism are also potential surrogates for catch-up growth in preterm infants.…”

Three‐dimensional in situ zonal morphology of viable growth plate chondrocytes: A confocal microscopy study

“…Hypertrophy (changes in cell volume and height), proliferation of chondrocytes as well as matrix synthesis have been implicated as the most important factors in both normal and mechanically modulated growth of long bones. 1,[12][13][14][15][16] It has been suggested that the final volume and shape of hypertrophic chondrocytes are important factors in determining the rate of longitudinal bone growth. The several-fold chondrocytic hypertrophy is believed to contribute to the major portion of long bone growth, with the remainder due to matrix synthesis in proliferative and hypertrophic zones as well as chondrocyte proliferation.…”

“…The several-fold chondrocytic hypertrophy is believed to contribute to the major portion of long bone growth, with the remainder due to matrix synthesis in proliferative and hypertrophic zones as well as chondrocyte proliferation. 6,10,11,14,15,17,18 According to Hunziker and Schenk, 6 the normal growth process of long bones is mostly controlled by the morphometric modulation of chondrocyte phenotype. A strong linear relationship was indeed established between hypertrophic chondrocytes volume and longitudinal bone growth rate in both tibial and radial growth plates of three animal species (rats, mice, and pigs).…”

“…Furthermore, cell volume regulation has been previously shown to influence matrix synthesis in cartilaginous tissue and would consequently have a significant impact on the integrity of the extracellular matrix, [20][21][22] suggesting that chondrocytic enlargement and matrix synthesis are strongly correlated. 15 Conventional histology and stereological techniques combined with chemical fixation have been used to characterize two-and three-dimensional growth plate morphometric parameters in different animal species both at tissue and cell levels. 2,3,6,8,9,19,23 In studies on the rat model at prepubertal, growth spurt, and mature developmental stages, it was demonstrated that, from the proliferative zone to the hypertrophic zone, chondrocyte volume enlarges up to 10-fold while chondrocyte height increases up to 5-fold.…”

Live Cell Imaging during Mechanical Stretch

“…Strong evidence also suggests that excessive tensile strain leads to direct injury to the alveolar epithelium, in addition to the biochemical responses of cells [11][12][13][14] . Although the focus here is primarily on the response of lung cells to mechanical deformation, pathways induced by mechanotransduction play a key role in the basic function of many tissues in the human body, including the regulation of vascular tone 15 and the development of the growth plate 16 .…”