Chondrocyte moves: clever strategies?

Abstract

Goals: To review the literature on chondrocyte movements and to develop plausible hypothesis for further work.

Design: Chondrocyte movements are herein defined as translocations of the cell body. A brief overview of cell migration in other cell types is presented to set the stage for a discussion of chondrocyte moves; this includes a discussion of the challenges that cells find when moving within tissues. Reports of isolated chondrocyte migration in vitro (isolated cell systems) and ex vivo (cartilage organ cultures) are then summarized, followed by a discussion of recent studies that infer chondrocyte movements in vivo.

Results: Investigators from different laboratories have observed chondrocyte motility in vitro. I became interested in the question of whether articular chondrocytes retained their phenotype during their migratory excursions. We devised a simple method to separate migratory and stationary chondrocytes and then showed that migratory chondrocytes synthesized collagen II but not I--consistent with a differentiated phenotype. Our time-lapse video microscopy studies showed that the cells displayed appropriate movement kinetics, albeit with low speed and directionality. Similarly, others have presented data consistent with slow movement of chondrocytes out of cartilage explants. It is important to decipher whether these in vitro movements reflect physiological states and if so, which events are simulated. Examples of in vivo studies that have inferred chondrocyte movements include those describing rotational or gliding movements of chondrocytes in the proliferative zone of the growth plate and its importance in the growth process; and the notion that chondrocytes move from the cartilage endplates to the nucleus pulposus (NP) in the spine of rabbits and rats during development. Such studies are consistent with the hypothesis that chondrocytes exhibit highly controlled and specialized movements during tissue growth and remodeling in vivo. On the other hand, the cartilage explant studies elicit interest in the possibility that matrix injuries resulting in disruption of the collagen network of adult cartilages provide a permissive environment for chondrocyte motility.

Conclusions: The case for in vivo chondrocyte motility remains to be proven. However, the in vitro and in vivo data on chondrocyte movements present an argument for further thought and studies in this area.

Figure 1. Individual Chondrocyte Videotracking

Example of a non-motile (panel A) and a motile cell (panel B). The cell images were captured at the times indicated. At each time, the shape of the cell is outlined. The cell at time 0 shows the superimposed outlines of the cell during subsequent movement captured from the individual frames shown in the different panels. The arrows show the direction of movement, and the inset on the lower right of each panel shows the cell trajectories. Copied from Chang C., Lauffenburger DA and Morales, T.I., OA and C, 2003.

Figure 2. Simplified Diagram of Proposed Proliferative Chondrocyte Movements in the Growth Plate

This diagram was prepared by the author (T.I.M.) with the aid of the MGH photolab from information the video 1 and discussion of the paper by Aszodi A, Hunziker EB, Brakebusch C and Fassler R, Genes and Development 2003, 17:2465-2479, after consultation with Drs Aszodi and Hunziker.

Figure 3. Simplified Diagram of Hypothetical Chondrocyte Movements in the Intervertebral Disc

The diagram was prepared by the author (T.I.M.) with the aid of the MGH photolab from information in the papers from Kim K-W, Lim T-H, Kim JG, Jeong S-T, Masuda K et al, Spine 2003 and Kim K-W, Ha k-Y, Park J-B, Woo Y-K, Chung H-N et al, Spine 2005 following consultation with Dr. An. NP=nucleus pulposus; CE=cartilage endplate; E= epiphysis; GP=growth plate. Note that the rabbit CE differed from what is reported for human CE. In the human, both the articular region and the growth plate are continuous in the CE. However, in rabbits, the articular region is separated gradually from the growth plate with the development of a secondary ossification center, an epiphysis. Please see ref. for an up to date review on the human intervertebral disc.