Klotho expression in osteocytes regulates bone metabolism and controls bone formation

Hirotaka Komaba, Jovana Kaludjerovic, Dorothy Z. Hu, Kenichi Nagano, Katsuhiko Amano, Noriko Ide, Tadatoshi Sato, Michael J. Densmore, Jun ichi Hanai, Hannes Olauson, Teresita Bellido, Tobias E. Larsson, Roland Baron, Beate Lanske

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Osteocytes within the mineralized bone matrix control bone remodeling by regulating osteoblast and osteoclast activity. Osteocytes express the aging suppressor Klotho, but the functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression in osteocytes as a potent regulator of bone formation and bone mass. Targeted deletion of Klotho from osteocytes led to a striking increase in bone formation and bone volume coupled with enhanced osteoblast activity, in sharp contrast to what is observed in Klotho hypomorphic (kl/kl) mice. Conversely, overexpression of Klotho in cultured osteoblastic cells inhibited mineralization and osteogenic activity during osteocyte differentiation. Further, the induction of chronic kidney disease with high-turnover renal osteodystrophy led to downregulation of Klotho in bone cells. This appeared to offset the skeletal impact of osteocyte-targeted Klotho deletion. Thus, our findings establish a key role of osteocyte-expressed Klotho in regulating bone metabolism and indicate a new mechanism by which osteocytes control bone formation.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - Dec 3 2016

Fingerprint

Osteocytes
Osteogenesis
Bone and Bones
Osteoblasts
Chronic Kidney Disease-Mineral and Bone Disorder
Bone Matrix
Bone Remodeling
Osteoclasts
Chronic Renal Insufficiency
Cultured Cells
Homeostasis
Down-Regulation

Keywords

  • Bone
  • FGF23
  • Hyperparathyroidism

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Komaba, H., Kaludjerovic, J., Hu, D. Z., Nagano, K., Amano, K., Ide, N., ... Lanske, B. (Accepted/In press). Klotho expression in osteocytes regulates bone metabolism and controls bone formation. Kidney International. https://doi.org/10.1016/j.kint.2017.02.014

Klotho expression in osteocytes regulates bone metabolism and controls bone formation. / Komaba, Hirotaka; Kaludjerovic, Jovana; Hu, Dorothy Z.; Nagano, Kenichi; Amano, Katsuhiko; Ide, Noriko; Sato, Tadatoshi; Densmore, Michael J.; Hanai, Jun ichi; Olauson, Hannes; Bellido, Teresita; Larsson, Tobias E.; Baron, Roland; Lanske, Beate.

In: Kidney International, 03.12.2016.

Research output: Contribution to journalArticle

Komaba, H, Kaludjerovic, J, Hu, DZ, Nagano, K, Amano, K, Ide, N, Sato, T, Densmore, MJ, Hanai, JI, Olauson, H, Bellido, T, Larsson, TE, Baron, R & Lanske, B 2016, 'Klotho expression in osteocytes regulates bone metabolism and controls bone formation', Kidney International. https://doi.org/10.1016/j.kint.2017.02.014
Komaba, Hirotaka ; Kaludjerovic, Jovana ; Hu, Dorothy Z. ; Nagano, Kenichi ; Amano, Katsuhiko ; Ide, Noriko ; Sato, Tadatoshi ; Densmore, Michael J. ; Hanai, Jun ichi ; Olauson, Hannes ; Bellido, Teresita ; Larsson, Tobias E. ; Baron, Roland ; Lanske, Beate. / Klotho expression in osteocytes regulates bone metabolism and controls bone formation. In: Kidney International. 2016.
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