Disruption of adolescent growth plate dynamics following removal of a putative chondrocyte mechanostat

AbstractBackgroundThe purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics predict those at risk of osteoarthritis.Methods8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was examined by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to GP bridging.ResultsHigher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely dispersed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes. 3-dimensional quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints.ConclusionsThe results confirm associations between aberrant chondrocyte hypertrophy marker expression and osteoarthritis pathology in a surgical and loaded murine model of osteoarthritis. Spatial variations in growth plate bridging formation revealed accelerated cartilage-bone transitions which may contribute to anatomical variation in vulnerability to osteoarthritis development in these models.

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Characterisation of growth plate dynamics in surgical and non-invasive loaded murine models of osteoarthritis

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2021.05.022 ◽

2021 ◽

Vol 29 ◽

pp. S12

Author(s):

H.J. Samvelyan ◽

K. Madi ◽

A.E. Törnqvist ◽

B. Javaheri ◽

K.A. Staines

Keyword(s):

Growth Plate ◽

Murine Models ◽

Non Invasive ◽

Plate Dynamics

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Effects of Hypophysectomy on the Occurrence and Calcifiability of Matrix Vesicles in the Epiphyseal Growth Plate of Immature Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002579 ◽

1980 ◽

Vol 38 ◽

pp. 578-579

Author(s):

S. I. Coleman ◽

W. J. Dougherty

Keyword(s):

Growth Plate ◽

Matrix Vesicles ◽

Epiphyseal Growth Plate ◽

Hard Tissue ◽

Hormonal Factors ◽

Post Surgery ◽

Mineral Deposition ◽

Thin Sectioning ◽

Integral Role ◽

Cellular Secretion

In the cellular secretion theory of mineral deposition, extracellular matrix vesicles are believed to play an integral role in hard tissue mineralization (1). Membrane limited matrix vesicles arise from the plasma membrane of epiphyseal chondrocytes and tooth odontoblasts by a budding process (2, 3). Nutritional and hormonal factors have been postulated to play essential roles in mineral deposition and apparently have a direct effect on matrix vesicles of calcifying cartilage as concluded by Anderson and Sajdera (4). Immature (75-85 gm) Long-Evans hooded rats were hypophysectomized by the parapharyngeal approach and maintained fourteen (14) days post-surgery. At this time, the animals were anesthetized and perfusion fixed in cacodylate buffered 2.5% glutaraldehyde. The proximal tibias were quickly dissected out and split sagittally. One half was used for light microscopy (LM) and the other for electron microscopy (EM). The halves used for EM were cut into blocks approximately 1×3 mm. The tissue blocks were prepared for ultra-thin sectioning and transmission EM. The tissue was oriented so as to section through the epiphyseal growth plate from the zone of proliferating cartilage on down through the hypertrophic zone and into the initial trabecular bone. Sections were studied stained (double heavy metal) and unstained.

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MICROCHEMICAL ANALYSIS OF HUMAN TIBIAL GROWTH CARTILAGE IN VARIOUS FORMS OF DWARFISM

Acta Endocrinologica ◽

10.1530/acta.0.0690659 ◽

1972 ◽

Vol 69 (4) ◽

pp. 659-688 ◽

Cited By ~ 16

Author(s):

V. Stanescu ◽

R. Stanescu ◽

J. A. Szirmai

Keyword(s):

Growth Plate ◽

Chondroitin Sulphate ◽

Epiphyseal Plate ◽

Molecular Characteristics ◽

Growth Disorders ◽

Normal Children ◽

Collagen Concentration ◽

Vitamin D Resistant Rickets ◽

Pooled Samples ◽

Tibial Epiphyseal

ABSTRACT Microchemical determinations of glycosaminoglycans and collagen were preformed in isolated histological zones from sections of tibial epiphyseal plate biopsies obtained from children with growth disorders (pituitary dwarfism, congenital myxoedema, Turner's syndrome, Noonan's syndrome, mucopolysaccharidosis type VI, vitamin D resistant rickets and achondroplasia). Alternate sections were used for histochemical localization of glycosaminoglycans and proteins. The values were compared with those found in comparable zones of the growth plate from normal children of the same age. The chondroitin sulphate concentration (% of defatted dry wt.) in the normal epiphyseal plate increased from the resting zone towards the proliferating/hypertrophic zone; collagen exhibited a reverse trend. In some of the pathological biopsies the concentration of chondroitin sulphate was slightly decreased whereas that of collagen was slightly increased. A marked increase in the collagen concentration was found in achondroplasia. The solubility profiles of the cetylpyridinium complexes of the chondroitin sulphate fraction showed three main peaks with slight but characteristic differences in the various zones of the normal cartilage plate. Significant shifts in the proportion of these peaks were observed in several pathological biopsies, indicating possible deviations from the normal molecular characteristics of the chondroitin sulphate. Analysis of the main chondroitin sulphate fraction, obtained from pooled samples of normal tibial growth plate after fractionation on the macroscale, indicated that all three peaks contained both chondroitin-4 sulphate and chondroitin-6 sulphate and that they probably differed in their molecular weight.

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