Mechanically modulated cartilage growth may regulate joint surface morphogenesis

Abstract

The development of normal joints depends on mechanical function in utero. Experimental studies have shown that the normal surface topography of diarthrodial joints fails to form in paralyzed embryos. We implemented a mathematical model for joint morphogenesis that explores the hypothesis that the stress distribution created in a functional joint may modulate the growth of the cartilage anlagen and lead to the development of congruent articular surfaces. We simulated the morphogenesis of a human finger joint (proximal interphalangeal joint) between days 55 and 70 of fetal life. A baseline biological growth rate was defined to account for the intrinsic biological influences on the growth of the articulating ends of the anlagen. We assumed this rate to be proportional to the chondrocyte density in the growing tissue. Cyclic hydrostatic stress caused by joint motion was assumed to modulate the baseline biological growth, with compression slowing it and tension accelerating it. Changes in the overall shape of the joint resulted from spatial differences in growth rates throughout the developing chondroepiphyses. When only baseline biological growth was included, the two epiphyses increased in size but retained convex incongruent joint surfaces. The inclusion of mechanobiological-based growth modulation in the chondroepiphyses led to one convex joint surface, which articulated with a locally concave surface. The articular surfaces became more congruent, and the anlagen exhibited an asymmetric sagittal profile similar to that observed in adult phalangeal bones. These results are consistent with the hypothesis that mechanobiological influences associated with normal function play an important role in the regulation of joint morphogenesis.

A comparison of the influence of global functional loads vs. local contact anatomy on articular cartilage thickness at the knee

“…The direct connection between local mechanical stress and cartilage thickness has not been reported in the literature, but computer simulation studies (Carter and Beaupre, 2001;Heegaard et al, 1999) and cell experimental studies (Smith et al, 1996(Smith et al, , 2000 support these results. Heegaard et al and Carter et al suggested that cartilage growth and morphology is regulated by hydrostatic pressure and octahedral shear stress (Carter and Beaupre, 2001;Heegaard et al, 1999). Smith et al showed that the chondrocyte metabolism varies according to the type of stresses and intermittent hydrostatic pressure increase type II collagen and aggrecan mRNA expression (Smith et al, 1996(Smith et al, , 2000.…”

“…During endochondral growth and ossification of bone rudiments, subchondral growth fronts under articular cartilage advance toward bone ends, forming the shape of the bone (Carter and Beaupre, 2001;Heegaard et al, 1999). Also, cartilage contact geometry, along with joint loading, can play an important role in determining local tissue stress (Han et al, 2005).…”

JNK/ERK–AP-1/Runx2 induction “paves the way” to cartilage load-ignited chondroblastic differentiation

“…This surface is greatly influenced by hydrostatic pressures generated during function due to joint loading (Beaupre et al 2000;Carter et al 1987;Smith et al 1992). Animal experiments and clinical studies with altered joint load (increased or decreased) support a causal relationship between cartilage function and form (Heegaard et al 1999;Pirttiniemi and Kantomaa 1998). While augmenting the functional loading of joints causes an increase in articular cartilage thickness, immobilization leads to a thinning of articular cartilage.…”

Temporal evolution of mechanical properties of skeletal tissue regeneration in rabbits: an experimental study

“…These interactions led to the theoretical concepts of mechanobiology [4,7]. The stress and strains applied to the precursor cells induce specific biological responses at all levels of the regenerating skeletal structure, from the molecular level of its extracellular matrix [9,20] to its macroscopic morphology [4,17].…”