Epigenetic regulation of osteoblastogenesis by blackcurrant fruit extracts in vitro and in vivo

Osteoporosis is a major public health concern and is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. Osteoporosis and osteopenia affect over 45 million Americans annually with an estimated cost of > $20 billion USD. Over 50% of women and ~13% of men over the age of 50 will suffer an osteoporosis‐related fracture in their lifetime resulting in loss of independence, health and productivity, thus the research and discovery of compounds that can enhance bone formation would be clinically significant. Blackcurrants ( Ribes nigrum ) are native to Central and Eastern Europe and Northern Asia and are used in traditional medicine for the treatment of cardiovascular disease, bone and muscle disorders, diabetes, viral infections and inflammation. The berries contain four major anthocyanins: delphinidin‐3‐O‐glucoside, delphinidin‐3‐O‐rutinoside, cyanidin‐3‐O‐glucoside, cyanidin‐3‐O‐rutinoside. We have previously shown that blackcurrant extracts (BCE) increase myoblastogenesis, and in this work, we investigate its effects in cultured hFOB human osteoblasts and osterix/Sp7:mCherry transgenic medaka. hFOB human osteoblasts were obtained from ATCC and cultured in 1:1 mixture of Ham's F12 Medium Dulbecco's Modified Eagle's medium, with 2.5 mM L‐glutamine (without phenol red). Double transgenic medaka (dT; osterix/Sp7 :mCherry were maintained at UIC under protocol #17‐166. Larvae at 9–12 dpf were staged and then treated for 5 days with the extracts and compounds (1–10 mg/ml). Osteoblast formation and distribution were analyzed by fluorescence microscopy, bone mineralization was visualized by calcein. The results of this investigation demonstrate that BCE and delphinidin‐3‐glucose increased osteoblast proliferation and reduced apoptosis in cultured human osteoblasts (hFOB) by reducing Bax and p53 expression and altering HDAC1, HDAC3, SIRT 3 and PGC1amRNA expression. In osterix/Sp7 :mCherry medaka, BCE treatment (10 mg/ml) increased osteoblast proliferation by increasing osterix/Sp7 expression. These data suggest that BCE and D3G increase osteoblastogenesis through epigenetic regulation of HDACs and mitochondrial biogenesis. Support or Funding Information NCCIH at the National Institutes of Health This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .