Cadmium Toxicity on Chondrocytes and the Palliative Effects of 1α, 25-Dihydroxy Vitamin D3 in White Leghorns Chicken's Embryo

Abstract

Cadmium (Cd) can causes osteoporosis and joint swelling. However, the mechanism of Cd toxicity in chondrocytes and how to alleviate Cd poisoning to chondrocytes are still unclear. Herein, we evaluated the toxicity of Cd to chicken chondrocytes, and whether vitamin D can relieve the toxicity of Cd to chondrocytes. Primary chondrocytes were collected from knee-joint cartilage of 15-day-old chicken embryos. They were treated with (0, 1, 2, and 4) μM Cd alone, 10−8 M 1α,25-(OH)2D3 alone, or 2 μM Cd combined with 10−8 M 1α,25-(OH)2D3. We found that Cd significantly inhibited Sox9 and ACAN mRNA expression, which are markers for chondrocyte differentiation, downregulated the mitochondrial membrane potential, upregulated the Bax/B-cell lymphoma 2 ratio. Furthermore, Cd significantly promoted matrix metalloproteinase (MMP)-9 expression, thus accelerating the degradation of extracellular matrix. And Cd also inhibited the expression of main macromolecular protein of extracellular matrix, Collagen type IIα1 (COL2A1) and acid mucopolysaccharide. However, 1α,25-(OH)2D3 pretreatment significantly alleviated the toxicity effects of Cd on the differentiation, apoptosis and extracellular matrix gene expression in primary chondrocytes. Conclusively, Cd exposure could inhibited chicken embryo chondrocytes differentiation, extracellular matrix gene expression, and induced chondrocyte apoptosis. However, these toxic effects of Cd are alleviated by the pretreatment of chondrocytes with 1α,25-(OH)2D3.

The Role of Galectin-3 in 1α,25(OH)2D3-Regulated Osteoclast Formation from White Leghorn Chickens In Vitro

“…RNA was extracted using Trizol (Thermo Fisher Scientific, Waltham, MA, USA) and qRT-PCR following the manufacturer’s instructions, as previously described [ 23 ]. The expression of the targeting genes cathepsin K ( CtsK ), TRAP , matrix metalloproteinase-9 ( MMP-9 ), carbonic anhydrase II ( CAII) , RANKL , osteoprotegrin ( OPG ), and Gal-3 mRNA was measured.…”

Experimental Study of Cadmium Accumulation in the Lower Jaw of Rats Under Conditions of Correction With Zinc and Iron Succinate

“…Studies by M. Watanabe et al (2003) also showed the possibility of Cd-induced formation of non-radical hydrogen peroxide H2O2, an important free radical source in Fenton reactions [10]. A set of studies conducted in the first twenty years of the 21st century showed that one of the important "targets" of cadmium's negative impact is bone and cartilage tissue: prolonged exposure to the toxicant leads to increased skeletal fragility and decreased bone mineral density [11,12]. In vivo studies in experimental animals have shown that chronic exposure to cadmium reduces the mineralisation of vertebral bodies, changing their biomechanical properties and making them more susceptible to deformation and fracture.…”

“…Дослідження M. Watanabe et al (2003) також показали можливість Cd-індукованого утворення нерадикального пероксиду водню H2O2, який є важливим джерелом вільних радикалів в реакціях Фентона [10]. Комплекс досліджень, виконаних в першому двадцятиріччі ХХІ століття, показав, що однією з важливих «мішеней» негативного впливу кадмію є кістково-хрящова тканина: тривала експозиція токсиканта на організм призводить до збільшення крихкості скелета та зниження мінеральної щільності кісток [11,12]. Дослідження in vivo на експериментальних тваринах показали, що хронічний вплив кадмію зменшує мінералізацію тіл хребців, змінюючи їх біомеханічні властивості та роблячи їх сприйнятливішими до деформації та руйнування.…”

The Impact of Trace Elements on Osteoarthritis

“…This is because cadmium easily displaces elements such as Fe 2+ and Cu 2+ in the membrane and cytosolic proteins and interacts with the sulfhydryl groups in the mitochondrial membrane proteins and antioxidants, such as catalase, glutathione and superoxide dismutase, thereby promoting the production of reactive oxygen species such as hydrogen peroxide and hydroxyl radicals ( 41 , 45 ). This results in production of interleukin-1β and interleukin-6, which activate matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) that destroy the extracellular matrix and affect the expression of aggrecan and type II collagen ( 46 ).…”