{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:37:25Z","timestamp":1791020245250,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2011,4,5]],"date-time":"2011-04-05T00:00:00Z","timestamp":1301961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, Hcy accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid (FA) in genetically HHcy\u2010associated decrease in bone blood flow and remodeling. Wild type (WT) and cystathionine\u2010\u03b2\u2010synthase heterozygous (CBS+\/\u2212) mice were used in this study and supplemented with or without FA (300\u2009mg\/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density (BD) was assessed by dual energy X\u2010ray absorptiometry. The bone homogenates were analyzed for oxidative stress, NOX\u20104 as oxidative marker and thioredoxin\u20101 (Trx\u20101) as anti\u2010oxidant marker, bone remodeling (MMP\u20109) and bio\u2010availability of nitric oxide (eNOS\/iNOS\/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+\/\u2212 mice. The BD was also reduced in CBS+\/\u2212 mice. There was an increase in NOX\u20104, iNOS, MMP\u20109 protein as well as MMP\u20109 activity in CBS+\/\u2212 mice and decrease in Trx\u20101, eNOS protein levels, in part by decreasing NO bio\u2010availability in CBS+\/\u2212 mice. Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss. \u00a9 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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