Thyroid hormone-induced chondrocyte terminal differentiation in rat femur organ culture

Wakita, Ryuji; Izumi, Toshihiro; Itoman, Moritoshi

doi:10.1007/s004410051127

Cited by 28 publications

(20 citation statements)

References 29 publications

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“…Sodium butyrate treatment resulted in hepatocytelike cells expressing glycolytic phenotype [115]. Thyroid hormones, steroid derivatives of cholesterol metabolism, have also been implicated as potent differentiation factors [116,117]. In addition, our recent findings indicate that glucosamine has chondrogenic effects on embryonic stem cells [118].…”

Section: Small Molecules-inmentioning

confidence: 66%

Controlled differentiation of stem cells

Hwang

Varghese

Elisseeff

2008

Advanced Drug Delivery Reviews

303

217

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The extracellular microenvironment plays a significant role in controlling cellular behavior. Identification of appropriate biomaterials that support cellular attachment, proliferation and, most importantly in the case of human embryonic stem cells, lineage-specific differentiation is critical for tissue engineering and cellular therapy. In addition to growth factors and morphogenetic factors known to induce lineage commitment of stem cells, a number of scaffolding materials, including synthetic and naturally-derived biomaterials, have been utilized in tissue engineering approaches to direct differentiation. This review focuses on recent emerging findings and well-characterized differentiation models of human embryonic stem cells. Additionally, we also discuss about various strategies that have been used in stem cell expansion.

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Section: Small Molecules-inmentioning

confidence: 66%

Controlled differentiation of stem cells

Hwang

Varghese

Elisseeff

2008

Advanced Drug Delivery Reviews

303

217

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“…D2 activity has been demonstrated in the embryonic growth plate where it is regulated by the skeletal morphogen Hedgehog (20). Nevertheless, D2 activity was not identified in primary chondrocytes, growth plate tissue extracts, or primary organ cultures from postnatal animals (19,(21)(22)(23), suggesting a discrete role during embryonic development. In osteoblasts data are conflicting (16,18,24), although specific D2 activity was identified in whole bone and differentiated MC3T3 osteoblastic cells in one study (17).…”

mentioning

confidence: 93%

Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

Bassett

Boyde

Howell

et al. 2010

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

131

135

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Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3′-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization.thyroid hormone metabolism | fracture | hypothyroidism | bone formation | skeleton T hyroid hormones are essential for linear growth and peak bone mass acquisition. In adults, thyrotoxicosis results in high bone turnover osteoporosis and increased susceptibility to fracture, whereas hypothyroidism reduces bone turnover (1-3). In previous studies, we identified thyroid hormone receptor α (TRα) as the critical mediator of 3,5,3′-L-triiodothyronine (T3) action in bone (4-7). The aim of this study is to investigate the role of the type 2 iodothyronine deiodinase (D2) as a local prereceptor modulator of T3 action in the skeleton.Thyroid hormone actions are determined by local availability of T3 to its nuclear receptor (8). D2 catalyzes removal of an outer ring 5′-iodine atom from the major circulating hormone thyroxine (T4) to generate the active metabolite T3. Conversely, the type 3 deiodinase (D3) inactivates both T4 and T3 by removal of an inner ring 5-iodine atom. Thus, D2 and D3, in conjunction with serum-derived T3, are important local modulators of thyroid hormone action in vivo. Expression of D2 and D3 is regulated in a temporo-spatial and tissue-specific manner, resulting in varying levels of T3 action in individual tissues despite relatively constant serum thyroid hormone levels (8).Mice deficient in D2 (D2KO) exhibit pituitary resistance to feedback regulation by T4 characterized by a 3-fold increase in serum thyroid-stimulating hormone (TSH), a 27% increase in the serum T4 level, but a normal T3 level. The increased TSH and T4 levels are evident as early as postnatal day (PD)10 (9). These changes are accompanied by cold intolerance, impaired hearing, and reduced brain T3 content (10). The type 1 deiodinase (D1) is widely believed to catalyze conversion of T4 to T3 in tissues such as liver and kidney, predominantly for export to plasma. Like the D2KO mice, D1/D2KO double-mutant mice exhibit increases in serum T4 and TSH and have a normal serum T3 level (10).The roles of D1 and D2 in regulating T3 action in the skeleton have not been studied, although limited information regarding growth is available. A minor and trans...

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“…In vivo, thyroid hormones regulate expression of parathyroid hormone related peptide (PTHrP) and PTHrP receptors, which control the pace of chondrocyte proliferation during endochondral ossification . In organ cultures, thyroxine (T 4 ) is a potent stimulator of chondrocyte differentiation (Wakita et al 1998, Miura et al 2002, whilst in vitro T 3 decreases the growth of chondrocyte colonies and inhibits cell proliferation (Bohme et al 1992, Ohlsson et al 1992, Okubo & Reddi 2003. Many investigators have also demonstrated a positive role for T 3 in regulating terminal differentiation of chondrocytes in vitro in several species using different culture systems (Ohlsson et al 1992, Quarto et al 1992, Ballock & Reddi 1994, Bohme et al 1995, Alini et al 1996, Leboy et al 1997, Ishikawa et al 1998, Okubo & Reddi 2003.…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor β

Rabier

Williams

Malléin-Gerin

et al. 2006

Journal of Endocrinology

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The active thyroid hormone, triiodothyronine (T 3 ), binds to thyroid hormone receptors (TR) and plays an essential role in the control of chondrocyte proliferation and differentiation. Hypo-and hyperthyroidism alter the structure of growth plate cartilage and modify chondrocyte gene expression in vivo, whilst TR mutations or deletions in mice result in altered growth plate architecture. Nevertheless, the particular roles of individual TR isoforms in mediating T 3 action in chondrocytes have not been studied and are difficult to determine in vivo because of complex cellular and molecular interactions that regulate growth plate maturation. Therefore, we studied the effects of TRa and TRb on chondrocyte growth and differentiation in primary cultures of neonatal rib chondrocytes isolated from TRa-and TRb-deficient mice. T 3 decreased proliferation but accelerated differentiation of rib chondrocytes from wild-type mice. T 3 treatment resulted in similar effects in TRa-deficient chondrocytes, but in TRbdeficient chondrocytes, all T 3 responses were abrogated. Furthermore, T 3 increased TRb1 expression in wild-type and TRa-deficient chondrocytes. These data indicate that T 3 -stimulated differentiation of primary rib chondrocytes in vitro requires TRb and suggest that the TRb1 isoform mediates important T 3 actions in mouse rib chondrocytes.

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Thyroid hormone-induced chondrocyte terminal differentiation in rat femur organ culture

Cited by 28 publications

References 29 publications

Controlled differentiation of stem cells

Controlled differentiation of stem cells

Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor β

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