Pathogenesis of ossification of ligamentum flavum might be associated with its stem cells

Abstract

Abstract Objective: Ossification of ligamentum flavum(OLF) is a process of endochondral ossification, but the study of its pathogenesis remains incomplete. Mesenchymal stem cells(MSCs) have multiple differentiation potential and they have been isolated in various human tissues. We aimed to deeply illustrate the role of ligament-like stem cells in the pathogenesis of OLF and provide new ideas for potential clinical treatment methods, and hopefully evaluate the progression and severity from another perspective..Methods: The morphological structure of ligamentum flavum ossification was observed by micro-CT. The osteogenic and chondrogenic differentiation markers were then detected through the staining sections of ligamentum flavum specimens. Immunohistochemical staining and flow cytometry were performed to observe the localization of MSCs in the ligamentum flavum. Moreover, gene expression microarray data were enriched to identify differentially expressed genes (DEGs) and key molecular events in OLF.Results: We found ectopic ossification and atrophic calcification of the mineralized structures in OLF. Osteogenic differentiation, lipogenic differentiation and chondrogenic differentiation occurred in OLF. GO, KEGG and GSEA results elucidated the possible tri-lineage differentiation process of MSCs during ligamentum flavum ossification from the GSE113212 dataset. In addition, CD44 and CD90-positive cells were significantly decreased in OLF tissues. CD44 and CD90-positive cells were enriched around the small blood vessels in the chondrogenic or inflammatory zones, indicating that MSCs were involved in the ossification progression of the ligamentum flavum.Conclusions: A tri-lineage differentiation exists in OLF. A class of ligamentum flavum-like stem cells with similar markers of MSCs can be isolated from ligamentum flavum tissues, which may be involved in the pathological progression of OLF.