Folic acid mitigated homocysteine‐mediated decrease in bone blood flow and bone remodeling

Abstract

Treatment with folic acid has been shown to decrease the risk of osteoporosis. Although homocysteine (Hcy) accumulated collagen in bone and contributed to decrease in bone strength and density, the mechanism of Hcy‐induced bone loss and collagen remodeling was unclear. To test the hypothesis that homocysteine‐mediated decrease in bone strength is in part due to decrease in bone blood flow and remodeling, we used wild type (WT) and hyperhomocysteinemia (cystathionine beta synthase heterozygote knockout, CBS−/+) mice treated with and without folic acid (FA 300 mg/kg in drinking water). The tibial arterial bone blood flow was measured by laser Doppler and ultrasonic flow probes. The tibial bone density was measured by a digital micrometer. The bone homogenates were analyzed for bone remodeling by measuring matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP). The results suggested that there was decrease in tibial arterial blood flow in CBS−/+ mice. The bone density was also reduced in CBS−/+ mice. There was increase in MMP‐2 and ‐9 protein level in CBS−/+ tibia. The levels of TIMP‐3 were increased, where TIMP‐4 was decreased in CBS−/+ tibia. Interestingly, the treatment with FA mitigated the decrease in TIMP‐4 in CBS−/+ tibia. We concluded that folic acid treatment mitigated the decrease in bone blood flow by increasing TIMP‐4 and strengthening the bone.