Prenatal Fumonisin Exposure Impairs Bone Development via Disturbances in the OC/Leptin and RANKL/RANK/OPG Systems in Weaned Rat Offspring

Abstract

The goal of the current study was to examine the effects of prenatal exposure to fumonisins (FBs) on bone properties and metabolism in weaned rat offspring divided into groups intoxicated with FBs at either 0 (the 0 FB group), 60 (the 60 FB group), or 90 mg/kg b.w. 0 (the 90 FB group). Female and male offspring exposed to FBs at a dose of 60 mg/kg b.w. had heavier femora. Mechanical bone parameters changed in a sex and FBs dose-dependent manner. Growth hormone and osteoprotegerin decreased in both sexes, regardless of FBs dose. In males osteocalcin decreased, while receptor activator for nuclear factor kappa-Β ligand increased regardless of FBs dose; while in females changes were dose dependent. Leptin decreased in both male FBs-intoxicated groups, bone alkaline phosphatase decreased only in the 60 FB group. Matrix metalloproteinase-8 protein expression increased in both female FBs-intoxicated groups and decreased in male 90 FB group. Osteoprotegerin and tissue inhibitor of metalloproteinases 2 protein expression decreased in males, regardless of FBs dose, while nuclear factor kappa-Β ligand expression increased only in the 90 FB group. The disturbances in bone metabolic processes seemed to result from imbalances in the RANKL/RANK/OPG and the OC/leptin systems.

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…The remaining 10% are non-collagenous proteins which significantly contribute to bone biological function; among them are plenty of ECM proteins, as well as growth factors and cytokines, such as osteonectin, osteopontin, osteocalcin, bone sialoprotein, fibronectin, vitronectin, matrix Gla protein (MGP), bone morphogenetic proteins (BMPs), alkaline phosphatase, and thrombospondin, as well as albumin and alpha-2-HS-glycoprotein [ 173 ]. Among factors playing a role in bone remodeling are osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), carbonic anhydrase II (CA II), cathepsin K, MMPs, and TIMPs [ 174 , 175 , 176 , 177 , 178 ]. Some proteins can be synthesized locally, whereas others are adsorbed from the circulation [ 173 ].…”