The Effects of Triiodothyronine on Human Osteoblast-Like Cells Metabolism and Interactions with Growth Hormone

Abstract

The expression of thyroid hormones receptors in osteoblasts and osteoclasts has involved these cells as direct targets for triiodothyronine (T3), but thyroid hormones may also interact with other hormones or local growth factors to exert their actions on bone cells. Among these, growth hormone (GH) is recognised as participating in the acquisition and maintenance of bone mass and exerting stimulatory effects on human osteoblastic cells. The aim of this study was to investigate T3 effects on primary human adult osteoblast-like cells (HOB) as well as to test for possible interactions between T3 and GH on bone cell metabolism. Primary human bone cell cultures were obtained by outgrowth from trabecular bone fragments from the hip and knee. Dose-response studies demonstrated enhanced [3H]-thymidine incorporation for T3 at 10(-9), 10(-8), 10(-7) and 20(-7) M, with a maximal response of 162.81 +/- 12.97 % with T3 10(-8) M, compared to vehicle (p < 0.001). Time-course studies showed an increased osteoblast-like cell proliferation after 24 h, followed by a decrease of cell proliferation by 48 h and 72 h of culture, respectively, when compared to control cells, with a maximal response after 72 h (T3 10(-10) M: 45.21 +/- 6.97 %, p < 0.01). In addition, T3 markedly increased specific alkaline phosphatase (AP) activity in HOB (10(-10) M: 169.86 +/- 12.14 % vs. control, p < 0.001), but no significant influence on type I procollagen propeptide (PICP) production was observed. At 10(-9) - 10(-7) g/ml, GH significantly enhanced HOB proliferation (p < 0.001) however, GH effects were not dose-dependent. Triiodothyronine, at a high concentration (10(-7) M), stimulated GH-receptor (GHR) mRNA levels by 165.20 +/- 16.54 % after 24 h (p < 0.05). Correspondingly, a synergistic effect of T 3 with the same concentration and GH on cell proliferation in human adult osteoblast-like cells was found.

Excess Maternal Thyroxine Alters the Proliferative Activity and Angiogenic Profile of Growth Cartilage of Rats at Birth and Weaning

“…61 It is likely that the thickness and percentage increase of trabecular bone in the offspring of rats treated with thyroxine may be due to increased osteogenic differentiation of stem cells promoted by thyroid hormones as demonstrated in vitro and in vivo . 13,62,63 So the increased bone apposition can also be explained by the direct influence of T 3 and T 4 on osteoblasts by stimulating the expression of proteins that are important for bone apposition, such as collagen X, alkaline phosphatase, 64 and osteocalcin. 65 In this study, excess thyroid hormone during pregnancy and lactation decreased VEGF expression in chondrocytes as shown by immunohistochemical and molecular analyses.…”

Thyroid Hormone and the Skeleton

“…Thyroid hormone directly stimulates osteoblast production of alkaline phosphatase [43,44], osteocalcin [24,45,46], osteoprotegerin [47], IGF-I [23], FGF receptor-1 [29], and matrix metalloproteinases [48,49]. These effects can be modulated by vitamin D and growth hormone [46,47,50,51].…”

Asian plants as a promising alternative to classic drugs in postmenopausal osteoporosis: A review of literature from clinical perspective

“…In a randomized, double-blind, placebocontrolled trial that enrolled 389 postmenopausal women with osteopenia, it was shown that genistein enhanced BMD by increasing urinary excretion of pyridinoline and deoxypyridinoline and increasing alkaline phosphatase and serum insulin-like growth factor (IGF)-1 levels (Marini et al, 2007). Apart from the systemic circulation, IGF-1 is abundantly found in both trabecular and cortical bone (Pepene et al, 2004a,b) to directly or indirectly mediate the effects of estrogens, parathyroid hormone, growth hormone and thyroid hormones (Pepene et al, 2001(Pepene et al, , 2003 and glucocorticoids (Pepene et al, 2010) on bone cells metabolism. To support isoflavones positive effects on bone via the IGF-1/IGF-1R pathway, it was reported that isoflavones extracted from Sophorae fructus, (Isocal ® ) are able to up-regulate the growth factors IGF-1 and transforming growth factor-ß in rat bone marrow cells (Joo et al, 2004).…”