Morphometric analysis of chondrocyte hypertrophy.

Buckwalter, J. A.; Mower, Donald A.; Ungar, Robin; Schaeffer, J; Ginsberg, Barry H.

doi:10.2106/00004623-198668020-00010

Cited by 173 publications

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“…5 Chondrocytes located at epiphyseal end of the proliferative zone divide rapidly while chondrocytes located at metaphyseal end of the proliferative columns start to increase in size towards the hypertrophic zone. [6][7][8][9][10][11] In the hypertrophic zone, cell division stops and terminal differentiation associated with a large increase in cell volume begins. 5 The mechanisms by which growth plate chondrocytes modulate longitudinal bone growth are still not well understood.…”

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confidence: 99%

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

Amini¹,

Veilleux²,

Villemure³

2010

Journal Orthopaedic Research

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Longitudinal growth, occurring in growth plates with structurally distinct zones, has clinical implications in the treatment of progressive skeletal deformities. This study documents the three-dimensional morphology of chondrocytes within histological zones of growth plate using confocal microscopy combined with fluorescent labeling techniques. Three-dimensional reconstruction of Calcein AMlabeled chondrocytes was made from stacks of confocal images recorded in situ from 4-week-old swine growth plates. Three-dimensional quantitative morphological measurements were further performed and compared at both tissue and cell levels. Chondrocyte volume and surface area increased about five-and threefold, respectively, approaching the chondro-osseous junction from the pool of reserve cells. Chondrocytes from the proliferative zone were the most discoidal cells (sphericity of 0.81 AE 0.06) among three histological zones. Minimum and maximum cell/matrix volume ratios were identified in the reserve (11.0 AE 2.2) and proliferative zones (16.8 AE 3.0), respectively. Evaluated parameters revealed the heterogeneous and zone-dependent morphological state of the growth plate. Tissue and cellular morphology may have noteworthy contribution to the growth plate behavior during growth process. The ability to obtain in situ cell morphometry and monitor the changes in the growth direction could improve our understanding of the mechanisms through which abnormal growth is triggered. ß

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confidence: 99%

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

Amini¹,

Veilleux²,

Villemure³

2010

Journal Orthopaedic Research

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“…Matrix synthesis occurs in all zones. During hypertrophy, cell volume increases approximately 5-to 10-fold (Buckwalter et al, 1986;Hunziker et al, 1987), and this volume increase is responsible for almost half of the increase in length of the long bone (Wilsman et al, 1996). Cranial synchondroses consist of two growth plates back-to-back, sharing a common resting zone, and are found in the cranial base.…”

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confidence: 99%

Endochondral ossification of the mouse nasal septum

2006

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Endochondral ossification at the caudal junctions of the cartilaginous nasal septum, in combination with interstitial expansion of the septum, is thought to displace the facial skeleton away from the neurocranium. However, the rate of endochondral ossification has not been measured or related to rates of septal enlargement. This study examined endochondral ossification at these junctions in mice from postnatal days 0-15, in the context of known cranial growth sites, the synchondroses. BrdU labeling was used to compare cell division at the septoethmoidal and septopresphenoidal junctions with cell division at the synchondroses, and double-fluorochrome labeling was used to measure mineralization rate. The results showed that the septoethmoidal and septopresphenoidal junctions develop the characteristic morphology of growth plates postnatally, and that the pattern of cell division is similar to that of synchondroses. Mineralization at these junctions occurred at rates that were not statistically different from those of the synchondroses. However, the cartilaginous septum increased in length much more rapidly than could be explained by caudal growth, implying that interstitial expansion is the more important contributor to septal growth.

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“…The intracellular volumes occupied by organelles and cytoplasmic ground substance gradually increase (Buckwalter et al 1986), together with the osmotic pressure generated by intracellular accumulation of organic osmolites (Farnum et al 2002). Although quantification of the effects of cellular electro-chemo-mechanical properties has proven difficult, it is apparent that this can only be partially responsible for the tenfold volume change and four to five times increased cell height during hypertrophy (Buckwalter et al 1986;Hunziker and Schenk 1989;Noonan et al 1998;Wilsman et al 1996). Interestingly, to keep up with such increase in cell height, the aligning extracellular matrix (ECM) needs to also stretch to 400-500% its original length.…”

Section: Introductionmentioning

confidence: 99%

“…The combined effect of changes in cell volume and matrix constitution is that the volume occupied by cells over the volume of ECM decreases from the early proliferative to the late hypertrophic zone. Yet, the total amount of matrix associated with one hypertrophic cell increases, with values ranging from 50 to 1000% depending on species, age and growth plate (Buckwalter et al 1986;Farnum et al 2002;Hunziker and Schenk 1989;Wilsman et al 1996) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…MMP's are abundant in quantity and diversity around hypertrophic cells, while these cells continue synthesizing collagen [review by (Ortega et al 2004)]. Consequently, the fraction of fibrillar collagen per volume of matrix from the upper proliferative to the lower hypertrophic zones in both the pericellular and interterritorial matrices increase in 4-5-month-old miniature pigs (Noonan et al 1998), but decrease in newborn mice (Buckwalter et al 1986). Collagen degradation in the hypertrophic zone decreases collagen-II fraction in bovine fetuses, associated with a loss of collagen network integrity, while collagen-X content increases (Alini et al 1992).…”

Section: Introductionmentioning

confidence: 99%

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Mechanics of chondrocyte hypertrophy

Donkelaar

Wilson

2011

Biomech Model Mechanobiol

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Chondrocyte hypertrophy is a characteristic of osteoarthritis and dominates bone growth. Intra-and extracellular changes that are known to be induced by metabolically active hypertrophic chondrocytes are known to contribute to hypertrophy. However, it is unknown to which extent these mechanical conditions together can be held responsible for the total magnitude of hypertrophy. The present paper aims to provide a quantitative, mechanically sound answer to that question. To address this aim requires a quantitative tool that captures the mechanical effects of collagen and proteoglycans, allows temporal changes in tissue composition, and can compute cell and tissue deformations. These requirements are met in our numerical model that is validated for articular cartilage mechanics, which we apply to quantitatively explain a range of experimental observations related to hypertrophy. After validating the numerical approach for studying hypertrophy, the model is applied to evaluate the direct mechanical effects of axial tension and compression on hypertrophy (Hueter-Volkmann principle) and to explore why hypertrophy is reduced in case of partially or fully compromised proteoglycan expression. Finally, a mechanical explanation is provided for the observation that chondrocytes do not hypertrophy when enzymatical collagen degradation is prohibited (S1Pcko knock-out mouse model). This paper shows that matrix turnover by metabolically active chondrocytes, together with externally applied mechanical conditions, can explain quantitatively the volumetric change of chondrocytes during hypertrophy. It provides a mechanistic explanation for the observation that collagen degradation results in chondrocyte hypertrophy, both under physiological and pathological conditions.

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Morphometric analysis of chondrocyte hypertrophy.

Cited by 173 publications

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

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

Endochondral ossification of the mouse nasal septum

Mechanics of chondrocyte hypertrophy

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