Different molecular weights seaweed Porphyra yezoensis polysaccharides inhibit hydroxyapatite damage and osteoblast differentiation on A7R5 cells
Vascular calcification (VC) is a common pathological manifestation in patients with cardiovascular disease, leading to high mortality in patients with chronic kidney disease. Deposition of hydroxyapatite (HAP) crystals on vascular smooth muscle cells lead to cell damage, which promotes osteogenic transformation. In this study, four different molecular weights (Mws) of Porphyra yezoensis polysaccharides (PYP1, PYP2, PYP3, and PYP4 with Mw of 576, 49.5, 12.6, and 4.02 kDa, respectively) were used to coat HAP, and differences in toxicity and calcification of HAP on A7R5 before and after coating were studied. The results showed that PYPs could effectively reduce HAP damage to A7R5 cells. Under the protection of PYPs, cell viability increased, lactate dehydrogenase release, active oxygen level, cell necrosis rate decreased, and the amount of HAP crystals adhering to cell surface and entering cells decreased. PYPs with low molecular weight presented better protective effect than high-molecular weight PYPs. PYPs also inhibited osteogenic transformation of A7R5 cells induced by HAP and decreased alkaline phosphatase (ALP) activity and expressions of bone/chondrocyte phenotype genes (Runt-related factor 2, ALP, osteopontin, and osteocalcin). In the adenine-induced chronic renal failure (CRF) mice VC model, PYP4 was found to obviously inhibit aortic calcium level, and also inhibit serum creatinine level, serum phosphorus level and serum BUN level. PYP4 (least molecular weight) showed the best inhibitory effect on calcification and may be considered a candidate drug with therapeutic potential for inhibiting cellular damage and osteoblast differentiation induced by HAP crystals.