Loss of Vlk in Prx1+ Cells Delays the Initial Steps of Endochondral Bone Formation and Fracture Repair in the Limb.
J Bone Miner Res
; 37(4): 764-775, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-35080046
ABSTRACT
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).
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Condrogénesis
Límite:
Animals
Idioma:
En
Revista:
J Bone Miner Res
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos