Abstract
Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Animals
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Antineoplastic Agents / pharmacology*
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Blotting, Western
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Cartilage, Articular / drug effects
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Cartilage, Articular / metabolism*
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Cartilage, Articular / pathology
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Cells, Cultured
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Chondrocytes / drug effects
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Chondrocytes / metabolism*
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Chondrocytes / pathology
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Female
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Humans
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Hypertrophy
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Immunoblotting
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Indans / pharmacology*
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Male
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Mice
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Mice, Knockout
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Middle Aged
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Organ Size
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Osteoarthritis, Knee / metabolism*
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Osteoarthritis, Knee / pathology
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / genetics*
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antineoplastic Agents
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Indans
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pterosin B
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Protein Kinases
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Protein Serine-Threonine Kinases
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SIK3 protein, human
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SIK3 protein, mouse