Induction and characterization of metallothionein in chicken epiphyseal growth plate cartilage chondrocytes

Sauer, Glenn R.; Nie, Daotai; Wu, Licia N.Y.; Wuthier, Roy E.

doi:10.1002/(sici)1097-4644(19980101)68:1<110::aid-jcb11>3.0.co;2-l

Cited by 8 publications

(1 citation statement)

References 39 publications

(26 reference statements)

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“…Several mechanisms have been suggested to be involved in causing the effects of CS on the ephiphyseal growth plate. Chief among these is inhibition of chondrocyte proliferation (31,32) and cartilage matrix production (33,34), which result in growth suppression (5). CS treatment of children is well known to cause growth retardation (4).…”

Section: Discussionmentioning

confidence: 99%

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure

Takahashi¹,

Wehrli²,

Hilaire³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Corticosteroids are in widespread clinical use but are known to have adverse skeletal side effects. Moreover, it is not known how soon these effects become apparent. Here, we describe a longitudinal approach to evaluate the short-term implications of excess corticosteroid exposure by quantitative in vivo magnetic resonance imaging and spectroscopy in conjunction with digital image processing and analysis in a rabbit model. Two-week treatment with dexamethasone induced a significant reduction in trabecular bone volume, which occurred at the expense of uniform trabecular thinning without affecting network architecture. Paralleling the loss in bone volume was conversion of hematopoietic to yellow marrow in the femoral metaphysis and atrophy of the femoral epiphyseal growth plate. This work demonstrates that detailed quantitative morphometric and physiological information can be obtained noninvasively at multiple skeletal locations. The method is likely to eventually replace invasive histomorphometry in that it obviates the need to sacrifice groups of animals at multiple time points. Finally, this work, which was performed on a clinical scanner, has implications for evaluating patients on high-dose steroid treatment.B one loss and concomitant fractures of the vertebrae and hip are common clinical consequences of corticosteroid (CS) treatment for inflammatory conditions (1). The overall incidence of osteopenia induced by treatment with CS for a period of less than 6 months is approximately 50% (2). Further, excess CS causes conversion of hematopoietic to fatty bone marrow (3). Besides bone loss, CS treatment is known to have multiple other skeletal implications and thus represents a major public health problem. Of particular concern are pediatric patients treated with high doses of CS (4, 5). Little, however, is known about the early response to supraphysiologic CS levels on the musculoskeletal system.Clinically, fracture risk is most commonly assessed on the basis of bone mineral density (BMD) measured with dual-energy x-ray bone absorptiometry (DEXA) or peripheral quantitative computed tomography (p-QCT). However, it is well known that BMD is not the sole determinant of bone strength and that architecture plays a significant role in conferring strength to the trabecular network (6-8). Unlike bone mineral densitometry, which affords a measure of global or regional bone density, we and others have shown that magnetic resonance microimaging ( -MRI) can quantify trabecular bone microarchitecture in vitro in specimens and biopsies (9-13) and in vivo in laboratory animals and humans (14-16). Whereas microcomputed tomography ( -CT) can generate high-resolution images of trabecular bone architecture (17), magnetic resonance (MR) is unique in that it is also able to provide detailed information on structure and function of soft tissues and bone marrow, which are also affected by steroid treatment.One of the difficulties of imaging microarchitecture in vivo is achievement of sufficient resolution and signal-to-noise ratio to...

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Section: Discussionmentioning

confidence: 99%

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure

Takahashi¹,

Wehrli²,

Hilaire³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes

Sauer

Smith

Cahalane

et al. 2003

J of Cellular Biochemistry

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Matrix vesicles released by epiphyseal growth plate chondrocytes are known to contain a significant quantity of labile Zn(2+). Zonal analysis of chicken metatarsal bones showed that the resting/proliferative region of the growth plate contained high levels of Zn(2+) with significantly lower levels in the hypertrophic cartilage suggesting a loss of cellular Zn(2+) as the chondrocytes mature. Intracellular labile Zn(2+) was measured in primary cultures of growth plate chondrocytes by assay with the fluorescent Zn-chelator toluenesulfonamidoquinoline (TSQ) and imaged by multi-photon laser scanning microscopy (MPLSM) with the TSQ derivative zinquin. Short-term exposure to Zn(2+), both in the presence and absence of pyrithione resulted in significant increases in cytosolic Zn(2+). Treatment with the membrane-permeant Zn(2+) chelator TPEN rapidly reduced the levels of labile Zn(2+) and triggered apoptosis. Cytosolic Zn(2+) levels were significantly reduced following 24-h incubations with known inducers of chondrocyte apoptosis. The loss of intracellular Zn(2+) was accompanied by a significant reduction in the cytosolic metal-binding protein metallothionein. Examination of Zn(2+)-treated cells with MPLSM showed uniformly higher zinquin fluorescence. Treatment of Zn(2+)-loaded cells with TPEN quenched zinquin fluorescence confirming that the observed fluorescence in chondrocytes is due to the presence of intracellular Zn(2+). A dose-dependent increase in zinquin fluorescence was observed in cells treated with a range of Zn(2+) concentrations. Short-term treatment of cultured chondrocytes with apoptosis-inducing chemicals resulted in transient increases in intracellular labile Zn(2+). These results indicate that Zn(2+) is mobilized from intracellular binding sites in the early stages of chondrocyte apoptosis and is subsequently lost from the cells. The early mobilization of Zn(2+) provides a mechanism for its movement to matrix vesicles and the extracellular matrix.

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Cell differentiation alters metallothionein expression in avian growth plate chondrocytes

Sauer

Nie

et al. 1999

Metallothionein IV

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Induction and characterization of metallothionein in chicken epiphyseal growth plate cartilage chondrocytes

Cited by 8 publications

References 39 publications

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure

In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure

Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes

Cell differentiation alters metallothionein expression in avian growth plate chondrocytes

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