ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 5.16 | DOI: 10.1530/ey.18.5.16

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Elife. 2020 Oct 16;9:e55212 Abstract:

In brief: In some species, growth plate and articular cartilage are not separated by secondary ossification centers. Here, the authors used mathematical modeling, ex vivo models and biophysical tests and indirectly demonstrate that secondary ossification centers evolved in order to protect the growth plate, and especially hypertrophic chondrocytes, from mechanical stress.

Comment: During development, the secondary ossification center (SOC) physically separates the initially contiguous growth plate and articular cartilage. However, the reason why these structures exist as separate entities is unclear. The evolutionary analysis used by Xie et al. demonstrated that SOC appeared during evolution in amniotes, when animals relocated their entire lifecycle to terrestrial environments, and this development often correlates with mechanical loads, as exemplified by the ossification pattern analysis in mammals with specialized extremities, such as whales, bats and jerboa, a species of bipedal hopping rodents.

The authors used mathematical modeling to investigate the influence of SOC on stress distribution within cartilage and found that SOC enhances the stiffness of epiphysis and reduces mechanical stress within the growth plates, preventing distortion and instability during locomotion. Using a combination of ex vivo models and biophysical tests, the authors show evidence suggesting that hypertrophic chondrocytes are the most sensitive cells to mechanical stress within the growth plate. Moreover, pharmacological and genetic manipulation of the SOC suggested that hypertrophic chondrocytes are protected by the SOC from apoptosis induced by extensive mechanical stress. Using atomic force microscopy, authors find that hypertrophic chondrocytes exhibit low stiffness, which may make them more sensitive to mechanical stress.

In summary, the authors used a combination of approaches and elegantly argue that the primary reason for the evolution of SOCs was the need to protect hypertrophic chondrocytes from mechanical stress and consequently that SOCs are critical to protect growth plates in growing children. The findings indicate that growth plate chondrocytes are critically sensitive to loading and that overloading may impair growth. The findings have direct implications for growing children’s participation in gymnastics and other sports that may cause extreme loading of growth plates.

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