Vertebral trabecular bone mechanical properties vary among functional groups of cetaceans

Since their appearance in the fossil record 34 Mya, modern cetaceans (dolphins, whales, and porpoises) have radiated into diverse habitats circumglobally, developing vast phenotypic variations among species. Traits such as skeletal morphology and ecologically-linked behaviors denote swimming activity; trade-offs in flexibility and rigidity along the vertebral column determine patterns of caudal oscillation. Here, we categorized 10 species of cetaceans (Families Delphinidae and Kogiidae; N = 21 animals) into functional groups based on vertebral centra morphology, swimming speeds, diving behavior, and inferred swimming patterns. We quantified trabecular bone mechanical properties (yield strength, apparent stiffness, and resilience) among functional groups and regions of the vertebral column (thoracic, lumbar, and caudal). We extracted 6 mm3 samples from vertebral bodies and tested them in compression in three orientations (rostrocaudal, dorsoventral, and mediolateral) at 2 mm min−1. Overall, bone from the pre-fluke/fluke boundary had the greatest yield strength and resilience, indicating that the greatest forces are translated to the tail during caudal oscillatory swimming. Group 1, composed of five shallow-diving delphinid species, had the greatest vertebral trabecular bone yield strength, apparent stiffness, and resilience of all functional groups. Conversely, Group 3, composed of two deep-diving kogiid species, had the least strong, stiff, and resilient bone, while Group 2 (three deep-diving delphinid species) exhibited intermediate values. These data suggest that species that incorporate prolonged glides during deep descents in the water column actively swim less, and place relatively smaller loads on their vertebral columns, compared with species that execute shallower dives. We found that cetacean vertebral trabecular bone properties differed from the properties of terrestrial mammals; for every given bone strength, cetacean bone was less stiff by comparison. This relative lack of material rigidity within vertebral bone may be attributed to the non-weight bearing locomotor modes of fully aquatic mammals.

RSPO3 is important for trabecular bone and fracture risk in mice and humans

With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.