title: The skeletal developmental toxicity of chlormequat chloride and its underlying mechanisms.
abstract: Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
authors.forename: Lanqin
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address: weidong_hao@126.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
mesh_terms: D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D002716:Chlormequat / Q000633:toxicity*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000097:blood; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D012863:Skeleton / Q000187:drug effects* / Q000254:growth & development; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016328:NF-kappa B; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D002716:Chlormequat; D013006:Growth Hormone
keywords: Chlormequat chloride; Growth hormone; Insulin-like growth factor-I; Skeletal development