title: Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.
abstract: Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 μg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.
authors: Department of Internal Medicine, Biomedical Research Institute, Seoul National University Hospital, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Mi-Gyeong
authors: MG
authors: Jang
authors: Department of Internal Medicine, Biomedical Research Institute, Seoul National University Hospital, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Ji Yeon
authors: JY
authors: Lee
authors: Department of Internal Medicine, Biomedical Research Institute, Seoul National University Hospital, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Jae-Yeon
authors: JY
authors: Yang
authors: Department of Internal Medicine, Biomedical Research Institute, Seoul National University Hospital, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Hyojung
authors: H
authors: Park
authors: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Jung Hee
authors: JH
authors: Kim
authors: Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors: Jung-Eun
authors: JE
authors: Kim
authors: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Chan Soo
authors: CS
authors: Shin
authors: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea.
authors: Seong Yeon
authors: SY
authors: Kim
authors: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul, 110-799, Republic of Korea. swkimmd@snu.ac.kr.|Department of Internal Medicine, Boramae Medical Center, Seoul National University, 20 Boramae-Ro 5-Gil, Dongjak-Gu, Seoul, 156-707, Republic of Korea. swkimmd@snu.ac.kr.
authors: Sang Wan
authors: SW
authors: Kim
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000097:blood / Q000378:metabolism; D000071538:Cortical Bone / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005819:Genetic Markers; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010521:Periosteum / Q000166:cytology / Q000187:drug effects*; D012886:Skull / Q000166:cytology / Q000187:drug effects; D013977:Tibia / Q000166:cytology / Q000187:drug effects
chemical_list: D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D010281:Parathyroid Hormone; C486031:Sost protein, rat
keywords: Anabolic action; Lineage-tracing study; Lining cell; Mature osteoblast