Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

Biochem Biophys Res Commun. 2012 Mar 30;420(1):108-13. doi: 10.1016/j.bbrc.2012.02.123. Epub 2012 Mar 3.

Abstract

A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of ≥ 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcification, Physiologic / drug effects
  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chondrocytes / cytology*
  • Chondrogenesis / drug effects*
  • Female
  • Male
  • Mice
  • Prolactin / pharmacology*
  • Prolactin / physiology
  • Proteoglycans / metabolism
  • Rats
  • Receptors, Prolactin / biosynthesis

Substances

  • Proteoglycans
  • Receptors, Prolactin
  • Prolactin