Notch and HES5 are regulated during human cartilage differentiation.

• The molecular mechanisms of cartilage differentiation are poorly understood. In a variety of tissues other than cartilage, members of the basic helix-loop-helix (bHLH) family of transcription factors have been demonstrated to play critical roles in differentiation. We have characterized the human bHLH gene HES5 and investigated its role during chondrogenesis. Blockage of the Notch signaling pathway with a gamma-secretase inhibitor has demonstrated that the human HES5 gene is a downstream marker of Notch signaling in articular chondrocytes. Markers for the Notch signaling pathway significantly decrease during cartilage differentiation in vitro. Cell proliferation assayed by using BrdU has revealed that blockage of Notch signaling is associated with significantly decreased proliferation. Northern blot and reverse transcription/polymerase chain reaction of a panel of various tissues have shown that HES5 is transcribed as a 5.4-kb mRNA that is ubiquitously expressed in diverse fetal and adult tissues. Articular cartilage from HES5(-/-) and wild-type mice has been analyzed by using various histological stains. No differences have been detected between the wild-type and HES5(-/-) mice. Our data thus indicate that the human HES5 gene is coupled to the Notch receptor family, that expression of Notch markers (including HES5) decreases during cartilage differentiation, and that the blockage of Notch signaling is associated with significantly decreased cell proliferation.

Ämnesord

NATURVETENSKAP  -- Matematik (hsv//swe)

NATURAL SCIENCES  -- Mathematics (hsv//eng)

Nyckelord

Adolescent

Adult

Animals

Basic Helix-Loop-Helix Transcription Factors

genetics

metabolism

Cartilage

Articular

cytology

metabolism

Cell Differentiation

Cells

Cultured

Chondrocytes

cytology

metabolism

Female

Gene Expression Regulation

physiology

Gene Silencing

Humans

Male

Mice

Mice

Knockout

Middle Aged

RNA

Messenger

metabolism

Receptors

Notch

antagonists & inhibitors

genetics

metabolism

Repressor Proteins

genetics

metabolism

Signal Transduction

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)