Osteolectin increases bone elongation and body length by promoting growth plate chondrocyte proliferation

Abstract

Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by Itga11 ), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While Osteolectin and Itga11 are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of Osteolectin associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that Osteolectin -deficient mice have shorter bones than those of sex-matched littermate controls. Integrin α11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin α11 as a regulator of bone elongation and body length in mice and humans.

The potential bone regeneration effects of leptin- and osteolectin-coated 3D-printed PCL scaffolds: an in vivo study

“…Bone grafting materials used in GBR can induce osteogenic performance, but loading osteogenic-inducing materials onto the scaffold is expected to further enhance bone formation. Therefore, in this study, bone regeneration was promoted by coating the scaffold with leptin and osteolectin, which are growth factors that stimulate osteogenic differentiation [38][39][40][41][42][43][44]. Adhesion and distribution of leptin and osteolectin were performed as previously described [51].…”

“…It also helps regulate the mineralization of bone tissue. Additionally, recent studies have shown that osteolectin binds to osteoporotic growth factors and promotes the activation of the Wnt pathway and the differentiation of bone marrow stromal cells, thus playing a role in maintaining the adult skeleton [42][43][44].…”

“…Osteolectin binds to integrin α11 (encoded by ltga11) to produce osteogenic growth factors that promote Wnt pathway activation by bone marrow stromal cells. These osteogenic growth factors include bone morphogenetic proteins (BMPs), insulin-like growth factors, fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGFs) [42][43][44]. Therefore, applying a leptin-and osteolectin-coated 3D-printed scaffold to the bone loss area might not only achieve a more stable implant placement but also improve bone regeneration and strengthen the surrounding area.…”