Does osteocytic SOST suppression mediate PTH bone anabolism?
Parathyroid hormone (PTH) has bone anabolic activity when administered intermittently, affecting cells of the osteoblastic lineage at various stages, yet much remains to be learned about precisely how PTH promotes osteoblastic bone formation. Recent discoveries revealed that PTH causes transcriptional suppression of the osteocyte marker gene SOST, which encodes the potent secreted bone formation inhibitor, sclerostin. This review addresses whether osteocytes, terminally differentiated cells of the osteoblastic lineage, which are entrapped within the mineralized bone matrix, contribute to PTH-induced bone formation responses via regulation of sclerostin levels, and discusses recent evidence on how the bone anabolic responses elicited by intermittent PTH treatment or by sclerostin inhibition overlap and diverge.
Kramer
Ina
I
Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
Keller
Hansjoerg
H
Leupin
Olivier
O
Kneissel
Michaela
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D005819:Genetic Markers; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C473449:PTH1R protein, human; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; C422903:SOST protein, human; D051153:Wnt Proteins