Involvement of matrix metalloproteinases in the growth plate response to physiological mechanical load

Abstract

Reich A, Simsa Maziel S, Ashkenazi Z, Monsonego Ornan E. Involvement of matrix metalloproteinases in the growth plate response to physiological mechanical load. J Appl Physiol 108: 172-180, 2010. First published October 22, 2009 doi:10.1152/japplphysiol.00821.2009.-Enzymes from the matrix metalloproteinase (MMP) family play a crucial role in growth-plate vascularization and ossification via proteolytic cleavage and remodeling of the extracellular matrix. Their regulation in the growth plate is crucial for normal matrix assembly. Endochondral ossification, which takes place at the growth plates, is influenced by mechanical loading. Using an in vivo avian model for mechanical loading, we have found increased blood penetration into the growth plates of loaded chicks. The purpose of this work was to study the involvement of MMP-2, -3, -9, -13, and -16 in the growth plate's response to loading and in the catch-up growth resulting from load release. We found that mechanical loading, as well as release from load, upregulated MMP-2, -9, and -13 expressions. In contrast, MMP-3, associated with cartilage injuries, and its associated protein connective tissue growth factor (CTGF), were downregulated by the load. However, after release from load, MMP-3 was upregulated and CTGF levels were elevated and caught up with the control. MMP-3 and CTGF were also downregulated after 60 min of mechanical stretching in vitro. These results demonstrate the central role of MMPs in the growth plate's response to mechanical loading, as well as in the catch-up growth followed load release.connective tissue growth factor; chondrocyte; extracellular matrix; matrix metalloproteinase THE LONG BONES OF THE FETAL skeleton develop through the process of endochondral ossification, in which cartilage serves as the initial skeletal element and is later replaced by bone (9). After birth, longitudinal growth occurs in the growth plates (57), which contain chondrocytes at different stages of differentiation, organized into several zones: resting, proliferative, prehypertrophic, and hypertrophic (16). During endochondral ossification, the cartilage, an avascular tissue, is gradually converted into a highly vascularized tissue, bone (42). This process is accompanied by changes in extracellular matrix (ECM) synthesis and remodeling mediated mainly by enzymes from the matrix metalloproteinase (MMP) family.The MMPs are a family of zinc-dependent proteases (4) that include collagenases, stromelysins, and gelatinases (54). Their substrates are the ECM proteins (32, 37), and they are involved in proteolytic cleavage and remodeling of the cartilage (59) and regulation of angiogenesis (48). Twenty-four distinct MMPs have been cloned in humans, but only MMP

Bone quality is affected by food restriction and by nutrition-induced catch-up growth

“…These results are supported by another study carried out by our research group, in which the effect of weight load on the growth plate of chicks was analyzed (Reich et al 2010). Using a completely different system for growth restriction and CU growth, it was found that during CU growth, concomitantly with an increase in EGP height, there was deterioration of the structural and mechanical characteristics of the skeleton suggesting that accelerated mineralization occurred in the EGP of the affected bones and that decelerated mineralization occurred during the CU period, when chondrogenesis is the dominant process.…”

“…Using a completely different system for growth restriction and CU growth, it was found that during CU growth, concomitantly with an increase in EGP height, there was deterioration of the structural and mechanical characteristics of the skeleton suggesting that accelerated mineralization occurred in the EGP of the affected bones and that decelerated mineralization occurred during the CU period, when chondrogenesis is the dominant process. These results suggest that the process may be more general than at first thought as it took place in both rats and chicken in very different experimental set-ups (Reich et al 2010). Of interest in this respect is the recent report on preterm infants, in which there was a significant decrease in bone strength during the first weeks of life, despite overall growth and weight gain (Eliakim et al 2009).…”

“…Morphometric analysis was performed using SkyScan Software (CTAn Software,v.1.11,SkyScan). 3D images (CTM file format) were constructed from the cortical and trabecular regions of interest, utilizing Marching Cubes 33 algorithm, using SkyScan Software (CTVol, SkyScan) (Reich et al 2010, Idelevich et al 2011.…”

1,25(OH)2D3 Alters Growth Plate Maturation and Bone Architecture in Young Rats with Normal Renal Function

“…Amplification was carried out using 7300 Fast Real-Time PCR System (Applied Biosystems). Gene expression was normalized to GAPDH and the data were analyzed using comparative 2 −ΔΔCt method [25].…”

Bone Gla Protein Increases HIF-1α–Dependent Glucose Metabolism and Induces Cartilage and Vascular Calcification

“…Additional morphometric parameters were calculated as suggested by recent guidelines for bone microstructure assessment using micro-CT. 31 3D images (CTM file format) were constructed from cortical and trabecular regions of interest, using Marching Cubes 33 algorithm in CTVol software. 32 …”