Details

Autor(en) / Beteiligte

• Lotinun, Sutada
• Ishihara, Yoshihito
• Nagano, Kenichi
• Kiviranta, Riku
• Carpentier, Vincent T
• Neff, Lynn
• Parkman, Virginia
• Ide, Noriko
• Hu, Dorothy
• Dann, Pamela
• Brooks, Daniel
• Bouxsein, Mary L
• Wysolmerski, John
• Gori, Francesca
• Baron, Roland

Titel

Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression

Ist Teil von

• The Journal of clinical investigation, 2019-08, Vol.129 (8), p.3058-3071

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness and mechanical properties. In addition, Ctsk deletion in osteocytes increased bone Parathyroid Hormone related Peptide (PTHrP), prevented the decrease in serum Parathyroid Hormone (PTH) induced by lactation, but amplified the increase in serum 1,25(OH)2D. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provides genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25-Dyhydroxyvitamin D (1,25(OH)2D), osteoclastogenesis and bone loss in response to the high calcium demand associated with lactation.