The initial modeling and subsequent development of the skeleton is controlled by complex gene-environment interactions. Biomechanical forces may be one of the major epigenetic factors that determine the form and differentiation of skeletal tissues. In order to test the hypothesis that static compressive forces are transduced into molecular signals during early chondrogenesis, we have developed a unique three-dimensional collagen gel cell culture system which is permissive for the proliferation and differentiation of chondrocytes. Mouse embryonic day 10 (E10) limb buds were microdissected and dissociated into cells which were then cultured within a collagen gel matrix and maintained for up to 10 days. Static compressive forces were exerted onto these cultures. The time course for expression pattern and level for cartilage specific markers, type II collagen and aggrecan, and regulators of chondrogenesis, Sox9 and IL-1beta, were analyzed and compared with non-compressed control cultures. Under compressive conditions, histological evaluation showed an apparent acceleration in the rate and extent of chondrogenesis. Quantitatively, there was a significant 2- to 3-fold increase in type II collagen and aggrecan expression beginning at day 5 of culture and the difference was maintained through 10 days of cultures. Compressive force also causes an elevated level of Sox9, a transcriptional activator of type II collagen. In contrast, the expression and accumulation of IL-1beta, a transcriptional repressor of type II collagen was down-regulated. We conclude that static compressive forces promote chondrogenesis in embryonic limb bud mesenchyme, and propose that the signal transduction from a biomechanical stimuli can be mediated by a combination of positive and negative effectors of cartilage specific extracellular matrix macromolecules.
Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells
I. Takahashi, G.H. Nuckolls, K. Takahashi, O. Tanaka, I. Semba, R. Dashner, L. Shum, H.C. Slavkin; Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells. J Cell Sci 30 July 1998; 111 (14): 2067–2076. doi: https://doi.org/10.1242/jcs.111.14.2067
Download citation file:
JCS Journal Meeting 2023: Imaging Cell Dynamics
Our 2023 Journal Meeting on ‘Imaging Cell Dynamics’ will be held from 14-17 May 2023 in Lisbon, Portugal. Due to popular demand, we can currently only accept applications for online attendance. Apply now to attend this meeting virtually. Registration deadline: 31 March.
Call for papers: Cell and Tissue Polarity
We are welcoming submissions for our next special issue, which will focus on ‘Cell and tissue polarity’ and will be guest edited by David Bryant. Submission deadline: 15 July.
Editorial: Publishing where it matters
Editor-in-Chief Michael Way outlines Journal of Cell Science’s plans for the upcoming year and introduces Seema Grewal as our new Executive Editor.
preLights 5th Birthday webinar
preLights, our preprint highlighting service, is celebrating its 5th birthday this year. To mark the occasion, join us online on 14 March 2023 at 16:00 GMT for a discussion, led by four preLights alumni, on how to identify and navigate the challenges and opportunities while shaping your career as an early-career researcher.
Cell Scientists to Watch
As a community-focused journal, Journal of Cell Science is keen to support the next generation of cell biologists. Check out Cell Scientists to Watch, our interview series featuring talented researchers who have recently set up their own labs.