Abstract
Growth plate chondrocytes undergo a coordinated process of differentiation, regulating long bone growth. Parathyroid hormone-like hormone (Pthlh) inhibits hypertrophic differentiation in the growth plate chondrocytes and reduces Hedgehog (Hh) signaling. In mice lacking the Hh mediator Suppressor of fused (Sufu), Pthlh treatment resulted in the up-regulation of Hh activity and an increased number of hypertrophic chondrocytes. Furthermore, Pthlh increased Sufu protein levels, and in chondrocytes lacking Sufu, it was unable to process Hh-regulated Gli transcription factors. Pthlh regulates chondrocyte differentiation and Gli activity in a Sufu-dependent manner, with Sufu acting as a molecular switch in its regulation of differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / physiology*
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Cells, Cultured
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Chondrocytes / cytology
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Chondrocytes / metabolism*
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Growth Plate / cytology
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Growth Plate / metabolism*
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism
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Mice
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Mice, Mutant Strains
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Parathyroid Hormone-Related Protein / genetics
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Parathyroid Hormone-Related Protein / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction / physiology*
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Zinc Finger Protein GLI1
Substances
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Gli1 protein, mouse
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Hedgehog Proteins
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Kruppel-Like Transcription Factors
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Parathyroid Hormone-Related Protein
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Repressor Proteins
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Sufu protein, mouse
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Zinc Finger Protein GLI1