Environmental Temperature Impact on Bone and Cartilage Growth

Abstract

Environmental temperature can have a surprising impact on extremity growth in homeotherms, but the underlying mechanisms have remained elusive for over a century. Limbs of animals raised at warm ambient temperature are significantly and permanently longer than those of littermates housed at cooler temperature. These remarkably consistent lab results closely resemble the ecogeographical tenet described by Allen's "extremity size rule," that appendage length correlates with temperature and latitude. This phenotypic growth plasticity could have adaptive significance for thermal physiology. Shortened extremities help retain body heat in cold environments by decreasing surface area for potential heat loss. Homeotherms have evolved complex mechanisms to maintain tightly regulated internal temperatures in challenging environments, including "facultative extremity heterothermy" in which limb temperatures can parallel ambient. Environmental modulation of tissue temperature can have direct and immediate consequences on cell proliferation, metabolism, matrix production, and mineralization in cartilage. Temperature can also indirectly influence cartilage growth by modulating circulating levels and delivery routes of essential hormones and paracrine regulators. Using an integrated approach, this article synthesizes classic studies with new data that shed light on the basis and significance of this enigmatic growth phenomenon and its relevance for treating human bone elongation disorders. Discussion centers on the vasculature as a gateway to understanding the complex interconnection between direct (local) and indirect (systemic) mechanisms of temperature-enhanced bone lengthening. Recent advances in imaging modalities that enable the dynamic study of cartilage growth plates in vivo will be key to elucidating fundamental physiological mechanisms of long bone growth regulation.