A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Tekijät: Sutada Lotinun, Yoshihito Ishihara, Kenichi Nagano, Riku Kiviranta, Vincent T. Carpentier, Lynn Neff, Virginia Parkman, Noriko Ide, Dorothy Hu, Pamela Dann, Daniel Brooks, Mary L. Bouxsein, John Wysolmerski, Francesca Gori, Roland Baron
Kustantaja: AMER SOC CLINICAL INVESTIGATION INC
Julkaisuvuosi: 2019
Journal: Journal of Clinical Investigation
Lehden akronyymi: J CLIN INVEST
Vuosikerta: 129
Numero: 8
Aloitussivu: 3058
Lopetussivu: 3071
Sivujen määrä: 14
ISSN: 0021-9738
eISSN: 1558-8238
DOI: https://doi.org/10.1172/JCI122936
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/42164640
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, we show that Ctsk deletion in osteocytes increased bone parathyroid hormone-related peptide (PTHrP) and prevented the decrease in serum parathyroid hormone (PTH) induced by lactation, but amplified the increase in serum 1,25-dyhydroxyvitamin D [1,25(OH)(2)D]. 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 provide genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25(OH)(2)D, osteoclastogenesis, and bone loss in response to the high calcium demand associated with lactation.
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