科研之友
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摘要
Type II collagen-positive(Col2+) cells have been reported as skeletal stem cells(SSCs), but the contribution of Col2+progenitors to skeletal development both prenatally and postnatally during aging remains unclear. To address this question, we generated new mouse models with ablation of Col2+cells at either the embryonic or postnatal stages. The embryonic ablation of Col2+progenitors resulted in the death of newborn mice due to a decrease in skeletal blood vessels, loss of all vertebral bones and absence of most other bones except part of the craniofacial bone, the clavicle bone and a small piece of the long bone and ribs,which suggested that intramembranous ossification is involved in long bone development but does not participate in spine development. The postnatal ablation of Col2+cells resulted in mouse growth retardation and a collagenopathy phenotype. Lineage tracing experiments with embryonic or postnatal mice revealed that Col2+progenitors occurred predominantly in the growth plate(GP) and articular cartilage, but a limited number of Col2+cells were detected in the bone marrow. Moreover, the number and differentiation ability of Col2+progenitors in the long bone and knee joints decreased with increasing age. The fate-mapping study further revealed Col2+lineage cells contributed to, in addition to osteoblasts and chondrocytes, CD31+blood vessels in both the calvarial bone and long bone. Specifically, almost all blood vessels in calvarial bone and 25.4% of blood vessels in long bone were Col2+lineage cells. However, during fracture healing, 95.5% of CD31+blood vessels in long bone were Col2+lineage cells. In vitro studies further confirmed that Col2+progenitors from calvarial bone and GP could form CD31+vascular lumens. Thus, this study provides the first demonstration that intramembranous ossification is involved in long bone and rib development but not spine development. Col2+progenitors contribute to CD31+skeletal blood vessel formation, but the percentage differs between long bone and skull bone. The number and differentiation ability of Col2+progenitors decreases with increasing age.
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