Thyroid hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances functional activities of mature osteoblasts in cultured rat calvaria cells

Ohishi, Keiji; Ishida, Hiroshi; Nagata, Toshihiko; Yamauchi, Noriyuki; Tsurumi, Chizuko; Nishikawa, Shingo; Wakano, Yoichi

doi:10.1002/jcp.1041610318

Cited by 50 publications

(40 citation statements)

References 45 publications

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“…This finding was described in adults rats with hyperthyroidism (14). According to some researchers, thyroid hormones stimulate osteoblast synthesis and, thus, the voluminous aspect observed in the osteoblasts of offspring of rats treated with thyroxin may be a reflex of this action (30,31). Besides, a recent study demonstrated that stem cells of the bone marrow of hyperthyroid female rats show greater potential for differentiation in osteoblasts (31), justifying the presence of areas of hyperplasia and the consequent increase in the percentage of trabecular bone tissue observed in animals in this study.…”

Section: Discussionmentioning

confidence: 70%

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

Maia

Santos

Batista

et al. 2016

Arch. Endocrinol. Metab.

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Objective: To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods: Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results: Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion: Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7

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Section: Discussionmentioning

confidence: 70%

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

Maia

Santos

Batista

et al. 2016

Arch. Endocrinol. Metab.

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“…Lack of this hormone or of its receptor results in severe developmental disturbances [36] but hyperthyroidism is known to increase bone cell functions and cause osteoporosis. At the cellular level, this hormone regulates many genes and their functions during the osteoblastic differentiation process like alkaline phosphatase and its activity [8,37] and OCN [7,9], and it additionally enhances the functional activity of differentiated osteoblasts [38]. The accelerated remodeling process encountered in hyperthyroidism could easily be explained by the fact that increased MMP-13 is synthesized thus enhancing the initiation of resorption.…”

Section: Discussionmentioning

confidence: 99%

Osteocalcin Attenuates T3- and Increases Vitamin D3-Induced Expression of MMP-13 in Mouse Osteoblasts

et al. 2009

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ates the T3 stimulated expression dose dependently in mouse osteoblasts [7] but shows a synergistic effect on the T3 regulation in rat osteosarcoma cells [9]. In human osteoblasts, T3 attenuates the 1,25D3-induced transcription of OCN [10,11]. Clinically, OCN, a marker protein of the mature osteoblasts, is routinely used as a serum marker for bone formation [12], as well as for bone turnover [13] and gains an increasing importance as a marker for malignancies such as prostate carcinoma [14,15] and leukemia [16].Recently, it was clearly demonstrated that the uncarboxylated form of OCN functions as a hormone regulating glucose metabolism and fat mass in mice [1]. It affects pancreatic ß-cell proliferation by regulating Cyclin D1 and Cdk4 expression. Moreover, OCN increases the expression of insulin as well as genes regulating adipocyte development and differentiation [17].Like OCN, MMP-13 (collagenase-3) has a double Abstract. Osteocalcin (OCN), the most abundant non-collagenous protein of the bone matrix, whose function is not fully understood, was recently suggested to act as endocrine factor regulating energy metabolism. Besides OCN, osteoblasts also express MMP-13, a matrix metallo-proteinase important for bone development and remodeling. Although differentially, both genes are regulated by 1,25-dihydroxy vitamin D3 (1,25D3) and T3, important hormones for bone metabolism. In mouse osteoblasts with a distinct differentiation status, T3 increases the expression of both proteins. By contrast, 1,25D3 stimulates the expression of MMP-13 but inhibits the expression of OCN in these cells. In humans, however, 1,25D3 upregulates both genes while T3 inhibits the OCN expression. using northern blot hybridization we studied gene expression in the mouse osteoblastic cell line MC3T3-e1. We show that MMP-13 expression was strongly increased by T3 when the stimulation of OCN was low and, inversely, that the MMP-13 increase was low when T3 strongly stimulated the OCN expression. These findings suggest an interrelationship between OCN and MMP-13 expression. In fact, we observed that externally added OCN attenuated the T3 induced MMP-13 expression dose dependently and, furthermore, increased the 1,25D3 stimulated MMP-13 expression. using a protein kinase A inhibitor we were able to show that this inhibitor mimics the effect of OCN suggesting a PKA dependent pathway to be involved in this regulatory process. We therefore hypothesize that OCN is a modulator of the hormonally regulated MMP-13 expression. [6,7]. By contrast, T3 -induced OCN-expression is specific for murine osteoblasts [7,8]. 1,25D3, however, attenu-

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“…Control of proliferation could depend on the state of differentiation, the culture time (Stein & Lian 1993, Ohishi et al 1994 or the development of cell/cell contacts. In this study, we seeded cells at different densities, cultured them for 3 days and studied DNA synthesis by measuring [ 3 H]thymidine incorporation.…”

Section: Discussionmentioning

confidence: 99%

Tri-iodothyronine inhibits multilayer formation of the osteoblastic cell line, MC3T3-E1, by promoting apoptosis

Varga¹,

Luegmayr²,

Fratzl‐Zelman³

et al. 1999

Journal of Endocrinology

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Cell death through apoptosis is a well-known mechanism for maintaining homoeostasis in many developmental and pathological processes. We have recently presented evidence for the occurrence of apoptosis during the formation of bone-like tissue in vitro. MC3T3-E1 osteoblast-like cells in culture develop features of the osteoblastic phenotype and form many cell layers embedded in extracellular matrix which can mineralise. Tri-iodothyronine (T 3 ), even though it enhances the expression of many osteoblastic features, attenuates the multilayer formation to about two layers. The aim of this study was to investigate how T 3 prevents multilayer formation. MC3T3-E1 cells were seeded at different densities and cultured for up to 2 weeks. Thereafter we analysed proliferation rate and the distribution of the phases of the cell cycle and studied apoptosis. We found that T 3 did not inhibit DNA synthesis. Analysis of the cell cycle phases showed an increase in the number of cells in G0/G1 with increasing cell density, but no significant effect of T 3 treatment was found. Morphological investigations showed apoptotic features in both cell layers and culture supernatants. The cells exhibited typical plasma membrane blebbings, chromatin condensation, DNA fragmentation and phagocytosed apoptotic bodies. T 3 treatment significantly increased the number of apoptotic cells. We conclude from our data that T 3 inhibits multilayer formation of MC3T3-E1 cells by increasing the rate of apoptosis and not by inhibition of proliferation. Because apoptosis is a fundamental regulatory event during bone tissue differentiation, our findings emphasise the importance of thyroid hormones in bone maintenance and development.

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Thyroid hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances functional activities of mature osteoblasts in cultured rat calvaria cells

Cited by 50 publications

References 45 publications

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

Osteocalcin Attenuates T3- and Increases Vitamin D3-Induced Expression of MMP-13 in Mouse Osteoblasts

Tri-iodothyronine inhibits multilayer formation of the osteoblastic cell line, MC3T3-E1, by promoting apoptosis

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