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Klotho expression in osteocytes regulates bone metabolism and controls bone formation
Hirotaka Komaba1, Jovana Kaludjerovic2, Dorothy Z Hu2
1Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, Massachusetts, USA; Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Kidney International
|April 12, 2017
Summary
Osteocytes regulate bone mass by expressing Klotho. Deleting Klotho from osteocytes boosts bone formation, while its overexpression inhibits it, revealing Klotho
Area of Science:
- Skeletal Biology
- Cellular Biology
- Endocrinology
Background:
- Osteocytes are key regulators of bone remodeling.
- The role of Klotho, an aging suppressor, in bone homeostasis is unclear.
Purpose of the Study:
- To investigate the function of Klotho expressed in osteocytes in regulating bone metabolism.
- To determine Klotho's impact on bone formation and mass.
Main Methods:
- Targeted deletion of Klotho in osteocytes.
- Overexpression of Klotho in cultured osteoblastic cells.
- Induction of chronic kidney disease to study Klotho in renal osteodystrophy.
Main Results:
- Osteocyte-specific Klotho deletion significantly increased bone formation and volume.
- Overexpression of Klotho inhibited osteoblast mineralization and activity.
- Chronic kidney disease downregulated Klotho in bone cells, offsetting deletion effects.
Conclusions:
- Osteocyte-expressed Klotho is a critical regulator of bone metabolism.
- Klotho in osteocytes controls bone formation and bone mass.
- This identifies a novel mechanism for osteocyte control over bone remodeling.