Embryonic movement stimulates joint formation and development: Implications in arthrogryposis multiplex congenita

Abstract

Arthrogryposis multiplex congenita (AMC) is a heterogeneous syndrome where multiple joints have reduced range of motion due to contracture formation prior to birth.A common cause of AMC is reduced embryonic movement in utero. This reduction in embryonic movement can perturb molecular mechanisms and signaling pathways involved in the formation of joints during development. The absence of mechanical stimuli can impair joint cavitation, resulting in joint fusion, and ultimately eliminate function. In turn, mechanical stimuli are critical for proper joint formation during development and for mitigating AMC. Studies in experimental animal models have provided a greater understanding on the molecular pathophysiology of congenital contracture formation as a consequence of embryonic immobilization. Elucidation of how the mechanical signaling environment is transduced to initiate a biological response will be necessary to gain a deeper understanding of how mechanical stimuli are intertwined in the molecular regulation of joint development.

Variation in human limb joint articular morphology

“…Understanding the responsiveness of external articular morphology to activity and loading, both during development and after maturation, is essential when considering sources of variation in joint morphology. The precise mechanisms of joint morphogenesis remain elusive, but researchers have suggested that a combination of biochemical and mechanical inputs are responsible for the morphological complexities of the adult joint (Carter & Wong, 1988; Chijimatsu & Saito, 2019; Frost, 1979; Hamrick, 1999; Plochocki et al, 2009; Rolfe et al, 2018; Zhou, 2021). Indeed, the main adaptive trajectories experienced during postnatal growth by the joint surfaces may be best explained by chondral modeling theory (Frost, 1979; Hamrick, 1999), which argues that varying degrees of hydrostatic pressure within the joint capsule shape the cartilage anlage so that the opposing articular surfaces remain semi‐congruent to one another in a way that maintains functional integrity of the joint.…”

Biofabrication of the osteochondral unit and its applications: Current and future directions for 3D bioprinting

“… 42 – 44 During embryonic development, joint movements ensure that the osteochondral interface is correctly formed and that chondrocytes become hypertrophic in the subchondral region. 45 , 46 Further in vitro research has also shown that 3D chondrocyte cultures have a phenotype closer to in vivo behaviour when subjected to intermittent dynamic loading. 47 In vitro 3D chondrocyte cell cultures have been subjected to a wide range of cyclic compressive strains, ranging from higher levels such as 10% 47 to lower 5% 44 and 1%–3%.…”

Covariance in human limb joint articular morphology

“…Presumably, the most proximate influence on joint morphology is the shape of neighboring morphology with which it must directly articulate (Carter & Wong, 1988; Chijimatsu & Saito, 2019; Zhou, 2021). For a joint to fulfill its functional role, its conarticular surfaces must grow into shapes and sizes that result in some degree of conformity.…”

“…Presumably, the most proximate influence on joint morphology is the shape of neighboring morphology with which it must directly articulate (Carter & Wong, 1988;Chijimatsu & Saito, 2019;Zhou, 2021).…”