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Loss of parafollicular cells during gravitational changes (microgravity, hypergravity) and the secret effect of pleiotrophin.

Albi E, Curcio F, Spelat R, Lazzarini A, Lazzarini R, Cataldi S, Loreti E, Ferri I, Ambesi-Impiombato FS - PLoS ONE (2012)

Bottom Line: We provide evidence that both microgravity and hypergravity induce similar loss of C cells with reduction of calcitonin production.Pleiotrophin over-expression result in some protection against negative effects of gravity change.Potential implication of the gravity mechanic forces in the regulation of bone homeostasis via thyroid equilibrium is discussed.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Nuclear Lipid BioPathology, Centro Ricerche Analisi Biochimico Specialistiche, Perugia, Italy.

ABSTRACT
It is generally known that bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space. Changes in blood flow, systemic hormones, and locally produced factors were indicated as important elements contributing to the response of osteoblastic cells to loading, but research in this field still has many questions. Here, the possible biological involvement of thyroid C cells is being investigated. The paper is a comparison between a case of a wild type single mouse and a over-expressing pleiotrophin single mouse exposed to hypogravity conditions during the first animal experiment of long stay in International Space Station (91 days) and three similar mice exposed to hypergravity (2Gs) conditions. We provide evidence that both microgravity and hypergravity induce similar loss of C cells with reduction of calcitonin production. Pleiotrophin over-expression result in some protection against negative effects of gravity change. Potential implication of the gravity mechanic forces in the regulation of bone homeostasis via thyroid equilibrium is discussed.

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Effect of the gravity change on thyroid tissue of WT animals.a) Morphology analysis of parafollicular thyroid cells. “vivarium 1”: mice maintained in vivarium cages (control for experiment in hypogravity); “hypogravity”: experimental mouse in space; “vivarium 2”: control for experiment in hypergravity; “hypergravity”: experimental mice in 2×g centrifuge. Hematoxylin-eosin staining, 40× magnification, 1 µm scale bar. F = follicle. b) Ratio between the number of follicular cells of three follicles delimiting a parafollicular area and the number of cells C in this area. The values are expressed as mean ± SD of three independent fields observed in duplicate (7 and 13 sections). (Significance, **P<0.001 space versus vivarium 1 and 2 g versus vivarium 2).
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pone-0048518-g001: Effect of the gravity change on thyroid tissue of WT animals.a) Morphology analysis of parafollicular thyroid cells. “vivarium 1”: mice maintained in vivarium cages (control for experiment in hypogravity); “hypogravity”: experimental mouse in space; “vivarium 2”: control for experiment in hypergravity; “hypergravity”: experimental mice in 2×g centrifuge. Hematoxylin-eosin staining, 40× magnification, 1 µm scale bar. F = follicle. b) Ratio between the number of follicular cells of three follicles delimiting a parafollicular area and the number of cells C in this area. The values are expressed as mean ± SD of three independent fields observed in duplicate (7 and 13 sections). (Significance, **P<0.001 space versus vivarium 1 and 2 g versus vivarium 2).

Mentions: We have previously demonstrated that while in the thyroid gland of WT control mice the follicles had variable size and spatial orientation, spaceflight animals presented a more homogenous thyroid tissue structure, with ordered follicles and reduction of interfollicular space [14]. Since most species C cells are mainly concentrated in the middle third of each thyroid lobe, the so-called C-cell region[15], we have focused the attention on this specific area. Our observations showed that in this area each interfollicular space is delimited by three follicles. Fig. 1a shows the particular of the walls of two adjacent follicles normally structured with numerous interfollicular cells in vivarium 1 (control for the space experiment). It is known that the follicle is surrounded by thyrocytes or follicular cells. The analysis of the cell number in vivarium 1 sample highlighted that the sum of the follicular cells of three follicles delimitating an interfollicular space is 78±9 whereas the number of C cells is 18±3. The ratio between the two cell types is reported in Fig. 1b. In space environment the interfollicular space is strongly reduced (Fig. 1a) and the number of follicular and C cells is 75±6 and 3±2 respectively, by increasing consequently their ratio (Fig. 1b). Thus it is clearly evident that the space environment induces a loss of C cells. To try to discriminate whether this effect was due to the reduction of gravity force or to other factors of the space environment we thought to repeat the experiments in hypergravity condition with the idea of obtaining or opposite results for the principle of opposites or similar results. This would open a whole issue related to the fact that any change of a physical force of gravity would have an impact on cellular function. The results have highlighted that the number of follicular and C cells in the control sample (vivarium 2) is 66±8 and 16±7 respectively, similar to those of vivarium 1 and consequently they have a similar ratio (Fig. 1b). In hypergravity conditions the number of follicular and C cells is 69±9 and 4±3 respectively, by increasing their ratio with respect to vivarium 2 (Fig. 1b). If you compare the results of hypo- and hypergravity it appears evident that they induce a similar effect on the reduction of C cells. Since thyroid C cells are mainly known for producing calcitonin we have performed immunohistochemical analysis with anti-calcitonin antibodies to test C cell function. The results show the immunopositivity in the central regions of the thyroid gland lobes, as expected, of vivarium 1 and vivarium 2 controls (Fig. 2a). Median and range values of surface area are 3,49 (3.86–3,39) mm2 and 2,77 (3,45–2,71) mm2 in the vivarium 1 and vivarium 2 respectively. Either in space sample or in 2 g sample the immunopositivity is strongly reduced (Fig. 2a) even if with different values. In fact, in the space environment the immunopositivity is evident in a surface equal to 0,019 (0,015–0,021) mm2 whereas in 2 g sample the value of surface is 0,39 (0,37–0,43). The ratio between the value of immunopositivity surface and total surface of the thyroid lobe is reported in Fig. 2b. Even if the number of cells C is similar in hypo- and hypergravity, the surface of the positive area to anti-calcitonin antibody is wider in hyper- than in hypogravity. This result allows to suppose that the few cells present are more active in hyper- than in hypogravity.


Loss of parafollicular cells during gravitational changes (microgravity, hypergravity) and the secret effect of pleiotrophin.

Albi E, Curcio F, Spelat R, Lazzarini A, Lazzarini R, Cataldi S, Loreti E, Ferri I, Ambesi-Impiombato FS - PLoS ONE (2012)

Effect of the gravity change on thyroid tissue of WT animals.a) Morphology analysis of parafollicular thyroid cells. “vivarium 1”: mice maintained in vivarium cages (control for experiment in hypogravity); “hypogravity”: experimental mouse in space; “vivarium 2”: control for experiment in hypergravity; “hypergravity”: experimental mice in 2×g centrifuge. Hematoxylin-eosin staining, 40× magnification, 1 µm scale bar. F = follicle. b) Ratio between the number of follicular cells of three follicles delimiting a parafollicular area and the number of cells C in this area. The values are expressed as mean ± SD of three independent fields observed in duplicate (7 and 13 sections). (Significance, **P<0.001 space versus vivarium 1 and 2 g versus vivarium 2).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526598&req=5

pone-0048518-g001: Effect of the gravity change on thyroid tissue of WT animals.a) Morphology analysis of parafollicular thyroid cells. “vivarium 1”: mice maintained in vivarium cages (control for experiment in hypogravity); “hypogravity”: experimental mouse in space; “vivarium 2”: control for experiment in hypergravity; “hypergravity”: experimental mice in 2×g centrifuge. Hematoxylin-eosin staining, 40× magnification, 1 µm scale bar. F = follicle. b) Ratio between the number of follicular cells of three follicles delimiting a parafollicular area and the number of cells C in this area. The values are expressed as mean ± SD of three independent fields observed in duplicate (7 and 13 sections). (Significance, **P<0.001 space versus vivarium 1 and 2 g versus vivarium 2).
Mentions: We have previously demonstrated that while in the thyroid gland of WT control mice the follicles had variable size and spatial orientation, spaceflight animals presented a more homogenous thyroid tissue structure, with ordered follicles and reduction of interfollicular space [14]. Since most species C cells are mainly concentrated in the middle third of each thyroid lobe, the so-called C-cell region[15], we have focused the attention on this specific area. Our observations showed that in this area each interfollicular space is delimited by three follicles. Fig. 1a shows the particular of the walls of two adjacent follicles normally structured with numerous interfollicular cells in vivarium 1 (control for the space experiment). It is known that the follicle is surrounded by thyrocytes or follicular cells. The analysis of the cell number in vivarium 1 sample highlighted that the sum of the follicular cells of three follicles delimitating an interfollicular space is 78±9 whereas the number of C cells is 18±3. The ratio between the two cell types is reported in Fig. 1b. In space environment the interfollicular space is strongly reduced (Fig. 1a) and the number of follicular and C cells is 75±6 and 3±2 respectively, by increasing consequently their ratio (Fig. 1b). Thus it is clearly evident that the space environment induces a loss of C cells. To try to discriminate whether this effect was due to the reduction of gravity force or to other factors of the space environment we thought to repeat the experiments in hypergravity condition with the idea of obtaining or opposite results for the principle of opposites or similar results. This would open a whole issue related to the fact that any change of a physical force of gravity would have an impact on cellular function. The results have highlighted that the number of follicular and C cells in the control sample (vivarium 2) is 66±8 and 16±7 respectively, similar to those of vivarium 1 and consequently they have a similar ratio (Fig. 1b). In hypergravity conditions the number of follicular and C cells is 69±9 and 4±3 respectively, by increasing their ratio with respect to vivarium 2 (Fig. 1b). If you compare the results of hypo- and hypergravity it appears evident that they induce a similar effect on the reduction of C cells. Since thyroid C cells are mainly known for producing calcitonin we have performed immunohistochemical analysis with anti-calcitonin antibodies to test C cell function. The results show the immunopositivity in the central regions of the thyroid gland lobes, as expected, of vivarium 1 and vivarium 2 controls (Fig. 2a). Median and range values of surface area are 3,49 (3.86–3,39) mm2 and 2,77 (3,45–2,71) mm2 in the vivarium 1 and vivarium 2 respectively. Either in space sample or in 2 g sample the immunopositivity is strongly reduced (Fig. 2a) even if with different values. In fact, in the space environment the immunopositivity is evident in a surface equal to 0,019 (0,015–0,021) mm2 whereas in 2 g sample the value of surface is 0,39 (0,37–0,43). The ratio between the value of immunopositivity surface and total surface of the thyroid lobe is reported in Fig. 2b. Even if the number of cells C is similar in hypo- and hypergravity, the surface of the positive area to anti-calcitonin antibody is wider in hyper- than in hypogravity. This result allows to suppose that the few cells present are more active in hyper- than in hypogravity.

Bottom Line: We provide evidence that both microgravity and hypergravity induce similar loss of C cells with reduction of calcitonin production.Pleiotrophin over-expression result in some protection against negative effects of gravity change.Potential implication of the gravity mechanic forces in the regulation of bone homeostasis via thyroid equilibrium is discussed.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Nuclear Lipid BioPathology, Centro Ricerche Analisi Biochimico Specialistiche, Perugia, Italy.

ABSTRACT
It is generally known that bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space. Changes in blood flow, systemic hormones, and locally produced factors were indicated as important elements contributing to the response of osteoblastic cells to loading, but research in this field still has many questions. Here, the possible biological involvement of thyroid C cells is being investigated. The paper is a comparison between a case of a wild type single mouse and a over-expressing pleiotrophin single mouse exposed to hypogravity conditions during the first animal experiment of long stay in International Space Station (91 days) and three similar mice exposed to hypergravity (2Gs) conditions. We provide evidence that both microgravity and hypergravity induce similar loss of C cells with reduction of calcitonin production. Pleiotrophin over-expression result in some protection against negative effects of gravity change. Potential implication of the gravity mechanic forces in the regulation of bone homeostasis via thyroid equilibrium is discussed.

Show MeSH
Related in: MedlinePlus