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Parathyroid Hormone Contributes to Regulating Milk Calcium Content and Modulates Neonatal Bone Formation Cooperatively with Calcium

Laboratory of Reproductive Medicine and The Research Center for Bone and Stem Cells (G.C., Z.G., Y.R., L.S., C.T., D.M.), Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, The People’s Republic of China; and Department of Medicine (A.K., D.G.), McGill University, Montreal, Quebec, Canada H3A 1A1

Address all correspondence and requests for reprints to: Dr. Dengshun Miao, Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, The People’s Republic of China. E-mail: dsmiao{at}njmu.edu.cn.

To determine whether PTH and calcium (Ca) interact in neonatal bone formation, female lactating mice either heterozygous (PTH^+/–) or homozygous (PTH^–/–) for targeted deletion of the pth gene were fed either a normal (1% Ca, 0.6% phosphate) or high-Ca diet (2% Ca and 0.4% phosphate). Dietary effects on milk Ca content and Ca-regulating hormones were determined in dams, and the effects of milk content were assessed on bone turnover in 3-wk-old pups. On the normal diet, milk Ca and 1,25-dihydroxyvitamin D₃ levels were lower, but milk PTH-related protein levels were higher in the PTH^–/– dams compared with the PTH^+/– dams. On the high-Ca diet, milk Ca levels were higher, but milk 1,25-dihydroxyvitamin D₃ and PTH-related protein levels were lower in both PTH^+/– and PTH^–/– dams. In pups fed by PTH^–/– dams compared with pups fed by PTH^+/– dams on normal diets, bone mineral density, trabecular bone volume relative to tissue volume, and the number of osteoblasts were reduced in both PTH^+/– (32.5 ± 1.2 vs. 39.6 ± 1.5 mg/cm², P < 0.05; 23.3 ± 1.6 vs. 29.2 ± 2.8%, P < 0.01; and 94.2 ± 8.2 vs. 123.5 ± 3.5/mm², P < 0.01, respectively) and PTH^–/– (20.4 ± 0.9 vs. 27.0 ± 1.2 mg/mm², P < 0.05; 16.8 ± 1.9 vs. 19.3 ± 2.1%, P < 0.05; and 48.6 ± 7.9 vs. 90.5 ± 8.6/mm², P < 0.01, respectively) pups but were lower in the PTH^–/– pups compared with the PTH^+/– pups. In contrast, in pups fed by either PTH^+/– or PTH^–/– dams on the high-Ca diet, bone mineral density, bone volume/tissue volume, and osteoblast numbers were significantly higher, in both PTH^+/– (50.5 ± 1.7 vs. 58.7 ± 2.0 mg/mm², P < 0.05; 37.9 ± 5.2 vs. 46.1 ± 5.1, P < 0.05; and 120.5 ± 9.2 vs. 159.3 ± 14.7/mm², P < 0.01, respectively) and PTH^–/– (33.0 ± 1.2 vs. 47.5 ± 2.2 mg/mm², P < 0.001; 23.8 ± 3.1 vs. 35.9 ± 2.0, P < 0.05; and 78.7 ± 10.1 vs. 99.8 ± 13.6/mm², P < 0.05, respectively), and were highest in the PTH^+/– pups fed by the PTH^+/– dams on the high-Ca diet. These results indicate that PTH can modulate Ca content of milk, and that PTH and Ca can each exert cooperative roles on osteoblastic bone formation in the neonate.