Unique Regenerative Mechanism to Replace Bone Lost During Dietary Bone Depletion in Weanling Mice.
The present study was undertaken to determine the mechanism whereby calcitropic hormones and mesenchymal stem cell progeny changes are involved in bone repletion, a regenerative bone process that restores the bone lost to calcium deficiency. To initiate depletion, weanling mice with a mixed C57BL/6 (75%) and CD1 (25%) genetic background were fed a calcium-deficient diet (0.01%) for 14 days. For repletion, the mice were fed a control diet containing 1.2% calcium for 14 days. Depletion decreased plasma calcium and increased plasma parathyroid hormone, 1,25(OH)2D (calcitriol), and C-terminal telopeptide of type I collagen. These plasma parameters quickly returned toward normal on repletion. The trabecular bone volume and connectivity decreased drastically during depletion but were completely restored by the end of repletion. This bone repletion process largely resulted from the development of new bone formation. When bromodeoxyuridine (BrdU) was administered in the middle of depletion for 3 days and examined by fluorescence-activated cell sorting at 7 days into repletion, substantial increases in BrdU incorporation were seen in several CD105 subsets of cells of osteoblastic lineage. When BrdU was administered on days 1 to 3 of repletion and examined 11 days later, no increases in BrdU were seen in these subsets. Additionally, osteocytes that stained positively for BrdU were increased during depletion. In conclusion, the results of the present study have established a unique regenerative mechanism to initiate bone repair during the bone insult. Calcium homeostatic mechanisms and the bone repletion mechanism are opposing functions but are simultaneously orchestrated such that both endpoints are optimized. These results have potential clinical relevance for disease entities such as type 2 osteoporosis.
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.
Matilda H-C
MH
Sheng
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.|Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California.
Kin-Hing William
KW
Lau
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.
Ram
R
Lakhan
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.
Abu Shufian Ishtiaq
ASI
Ahmed
Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California.
Charles H
CH
Rundle
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.
Patra
P
Biswanath
Regenerative Medicine Division, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California.
David J
DJ
Baylink
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood / Q000172:deficiency*; D002136:Calcium, Dietary; D024042:Collagen Type I / Q000097:blood; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000502:physiology*; D010281:Parathyroid Hormone / Q000097:blood*; D010455:Peptides / Q000097:blood; D012038:Regeneration / Q000502:physiology*
D002136:Calcium, Dietary; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D002117:Calcitriol; D002118:Calcium