Loss of Vlk in Prx1+ Cells Delays the Initial Steps of Endochondral Bone Formation and Fracture Repair in the Limb.

Vertebrate lonesome kinase (Vlk) is a secreted tyrosine kinase important for normal skeletogenesis during embryonic development. Vlk null mice (Vlk-/- ) are born with severe craniofacial and limb skeletal defects and die shortly after birth. We used a conditional deletion model to remove Vlk in limb bud mesenchyme (Vlk-Prx1 cKO) to assess the specific requirement for Vlk expression by skeletal progenitor cells during endochondral ossification, and an inducible global deletion model (Vlk-Ubq iKO) to address the role of Vlk during fracture repair. Deletion of Vlk with Prx1-Cre recapitulated the limb skeletal phenotype of the Vlk-/- mice and enabled us to study the postnatal skeleton as Vlk-Prx1 cKO mice survived to adulthood. In Vlk-Prx1 cKO adult mice, limbs remained shorter with decreased trabecular and cortical bone volumes. Both Vlk-Prx1 cKO and Vlk-Ubq iKO mice had a delayed fracture repair response but eventually formed bridging calluses. Furthermore, levels of phosphorylated osteopontin (OPN) were decreased in tibias of Vlk-Ubq iKO, establishing OPN as a Vlk substrate in bone. In summary, our data indicate that Vlk produced by skeletal progenitor cells influences the timing and extent of chondrogenesis during endochondral bone formation and fracture repair. © 2022 American Society for Bone and Mineral Research (ASBMR).

The promise and challenge of cancer microbiome research.

Many microbial agents have been implicated as contributors to cancer genesis and development, and the search to identify and characterize new cancer-related organisms is ongoing. Modern developments in methodologies, especially culture-independent approaches, have accelerated and driven this research. Recent work has shed light on the multifaceted role that the community of organisms in and on the human body plays in cancer onset, development, detection, treatment, and outcome. Much remains to be discovered, however, as methodological variation and functional testing of statistical correlations need to be addressed for the field to advance.