Type II collagen-positive progenitors are important stem cells in controlling skeletal development and vascular formation

Abstract

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.

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

“…The same groups presented localized areas of bone remodeling (woven bone), which were heavily stained for COL I and less reactive at the bone chip remnants ( Figures 6B2, B4 —red dashed lines). These fragments of the original bone graft ( Figures 6C2, C4 —red dashed lines), identified by the presence of islands of hypermineralized cartilage, were positively stained for collagen type II ( Figures 6C2, C4 ), suggesting osteochondral bone formation ( Li et al, 2022 ). Nevertheless, the bone chips positively stained for osteocalcin (OC), a late osteogenic marker of bone formation, expressed by early osteocytes, as well as at bone lining osteoblasts at the surface of the bone chips ( Figure 6D2 —red arrows; Figure 6D4 ).…”

β-catenin inhibition disrupts the homeostasis of osteogenic/adipogenic differentiation leading to the development of glucocorticoid-induced osteonecrosis of the femoral head

“…Besides of the similar parts with Osx + cells (osteoblasts, osteocytes and stromal cells underneath growth plate), Col2 + cells also largely expressed in the chondrocytes of articular cartilage, secondary ossification center and growth plate. Whether these Col2 + chondrocytes in secondary ossification center and growth plate caused this GONFH-like phenotype, as it has been reported that the osteogenic commitment of these Col2 + chondrocytes (Shu et al, 2021 ;Li et al, 2022 ). At the age of 3 month, Col2 + chondrocytes in the secondary ossification center and growth plate were almost replaced by Col2 + osteoblasts, osteocytes and stromal cells, while GONFH-like phenotype including fat droplets accumulation and sparse bone trabeculae could be still observed in 6-month-old β-catenin Col2ER mice, indicating that not only Col2 + chondrocytes but all Col2 + cells in different cellular morphology were involved in this GONFH-like phenotype.…”

Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function

“…Sirius red staining indicates that lack of Sfrp4 leads to a disorganization of collagen fibrils in cortical bone and fracture experiments show that lack of Sfrp4 hinders the periosteal response to bone fracture and callus formation and this was associated with a decrease in the Ctsk-lineage cells. Previous studies have reported that Col2a1 + cells in bone marrow, growth plate and perichondrial/periosteal are skeletal stem cells, and genetic lineage tracing studies, have recently shown that embryonic Col2a1 + cells contribute to cells in the growth plate, trabecular or cortical bone, tendons, and ligaments ( 68 – 72 ). Our findings that Col2a1 expression is decreased in Sfrp4 -deficient Ctsk-lineage PSCs, are therefore consistent with our hypothesis that absence of Sfrp4 negatively affects the differentiation and functionality of these cells.…”