Short-term intermittent administration of parathyroid hormone facilitates osteogenesis by different mechanisms in cancellous and cortical bone
Kenji Ogura,
Tadahiro Iimura,
Yuji Makino,
Ayano Sugie-Oya,
Aya Takakura,
Ryoko Takao-Kawabata,
Toshinori Ishizuya,
Keiji Moriyama,
Akira Yamaguchi
Affiliations
Kenji Ogura
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
Tadahiro Iimura
Division of Bio-Imaging, Proteo-Science Center (PROS), Ehime University, Ehime 791-0295, Japan
Yuji Makino
Department of Orthopedics, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo 136-0075, Japan
Ayano Sugie-Oya
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan
Aya Takakura
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan
Ryoko Takao-Kawabata
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan
Toshinori Ishizuya
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan
Keiji Moriyama
Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
Akira Yamaguchi
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; Oral Health Science Center, Tokyo Dental College, Tokyo 101-0061, Japan; Corresponding author at: Oral Health Science Center, Tokyo Dental College, Tokyo 101-0061, Japan.
Intermittent administration of human parathyroid hormone (1–34)[hPTH(1–34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1–34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1–34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1–34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5. Injections of hPTH(1–34) induced no significant changes in the number of sclerostin-positive osteocytes in the cancellous bone. In the cortical bone, intermittent administration of hPTH(1–34) significantly reduced the number of sclerostin-positive osteocytes. The serum sclerostin level was downregulated and the osteocalcin level was upregulated on day 5 after intermittent administration of hPTH(1–34). Intermittent hPTH(1–34) injections increased osteoblast surface, osteoid thickness, and osteoid surface in cancellous bone, but not in cortical bone. This study suggested that the increase in osterix-positive osteoprogenitors in cancellous bone and the decrease in sclerostin-positive osteocytes in cortical bone play important roles in anabolic action on osteogenesis induced by short-term administration of hPTH(1–34). Keywords: PTH, Osteogenesis, Osterix, Sclerostin, Cortical bone, Cancellous bone