Utjecaj serotoninemije na metabolizam koštane pregradnje [Effect of serotoninemia on bone remodeling metabolism]

Erjavec, Igor (2014) Utjecaj serotoninemije na metabolizam koštane pregradnje [Effect of serotoninemia on bone remodeling metabolism]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The mechanism of serotonin (5-HT) effect on bone is still unclear. In this research the effect of altered 5-HT homeostasis on bone was further investigated in WZ-5HT rat model. Mineral density and bone parameters of femur and 3rd lumbar vertebrae were resolved using DXA and micro CT, respectively. Elevated blood 5-HT caused increased body weight and bone growth in WZ-5HT rats. Cortical bone had increased periosteal formation and endosteal resorption in animals from 5HT-high subline. Sigificant increase in bone formation rate follwed by increase in bone resorption marker indicate high bone remodelling in high-5HT rats, which decreased trabecular bone at the site of distal femur and lubar spine. Fracture healing was delayed in high-5HT animals due to prolonged mineralization of bone callus. Animals with elevated 5-HT level had decreased level of 1,25(OH)2D3 and they developed hyperglycemia, hyperinsulinemia and increased accumulation of visceral fat tissue with ageing, a symptoms of diabetes melitus type II phenotype development. In osteoblasts and osteoclasts neither 5-HT nor insulin had effect, while their sinergistic effect caused increased differentiation of osteoblasts and decreased differentiation of osteoclasts, respectively. It has been shown that 5-HT exerts its effect on bone together with insulin promoting osteoblast activation which in turn activates osteoclasts and increases bone turnover.

Abstract in Croatian

Mehanizam djelovanja serotonina (5-HT) na koštano tkivo nije u potpunosti razjašnjen. U ovom radu istražen je utjecaj promijenjene homeostaze 5-HT-a na koštano tkivo u WZ-5HT štakorskom modelu. Mineralna gustoća i koštani parametri bedrene kosti i 3. lumbalnog kralješka izmjereni su DXA i mikro CT uređajima. Povećana aktivnost 5-HT sustava u WZ-5HT štakora uzrokovala je povećanu tjelesnu masu i rast kostiju. Kod kortikalne kosti primjećeno je povećano periostalno širenje i endostealna resorpcija u životinja iz 5HT-visoke sublinije. Značajno povećana stopa koštanog stvaranja, uz povišenu koncentraciju markera koštane razgradnje, upućuju na povećanje koštane pregradnje u štakora iz 5HT-visoke sublinije. Visoka stopa koštane pregradnje uzrokovala je smanjenje trabekularne kosti distalne bedrene kosti i lumbalnog dijela kralješnice u tih životinja. U štakora iz 5HT-visoke sublinije je cijeljenje prijeloma bilo usporeno zbog smanjene mineralizacije koštanog kalusa. Životinje s povišenom količinom 5-HT-a imale su smanjenu količinu 1,25(OH)2D3 te su starenjem razvile hiperglikemiju, hiperinzulinemiju i povećano nakupljanje visceralnog masnog tkiva, što su indikatori razvoja fenotipa dijabetesa melitusa tipa II. Pojedinačno, 5-HT i inzulin nisu pokazali učinak na osteoblaste i osteoklaste, ali zajedno su sinergistički pojačali diferencijaciju osteoblasta i smanjili diferencijaciju osteoklasta. Pokazano je da 5-HT djeluje na koštano tkivo u sinergiji s inzulinom potičući aktivaciju osteoblasta koji dalje aktiviraju osteoklaste i tako povećavaju koštanu pregradnju.

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