Role of Primary Cilia in Skeletal Disorders

Abstract

Primary cilia are highly conserved microtubule-based organelles that project from the cell surface into the extracellular environment and play important roles in mechanosensation, mechanotransduction, polarity maintenance, and cell behaviors during organ development and pathological changes. Intraflagellar transport (IFT) proteins are essential for cilium formation and function. The skeletal system consists of bones and connective tissue, including cartilage, tendons, and ligaments, providing support, stability, and movement to the body. Great progress has been achieved in primary cilia and skeletal disorders in recent decades. Increasing evidence suggests that cells with cilium defects in the skeletal system can cause numerous human diseases. Moreover, specific deletion of ciliary proteins in skeletal tissues with different Cre mice resulted in diverse malformations, suggesting that primary cilia are involved in the development of skeletal diseases. In addition, the intact of primary cilium is essential to osteogenic/chondrogenic induction of mesenchymal stem cells, regarded as a promising target for clinical intervention for skeletal disorders. In this review, we summarized the role of primary cilia and ciliary proteins in the pathogenesis of skeletal diseases, including osteoporosis, bone/cartilage tumor, osteoarthritis, intervertebral disc degeneration, spine scoliosis, and other cilium-related skeletal diseases, and highlighted their promising treatment methods, including using mesenchymal stem cells. Our review tries to present evidence for primary cilium as a promising target for clinical intervention for skeletal diseases.

Microstructure changes and miRNA-mRNA network in a developmental dysplasia of the hip rat model

“…The direction of the cilia affects the growth direction on the growth plate, and chondrocytes with cilium defects in the skeletal system can cause numerous human diseases. 28 Therefore, MAP2 may be a promising target for clinical interventions in DDH. ZRSR2 is an essential factor that recognizes 30 splicing sites during pre-mRNA splicing.…”

Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis

“…Scoliosis is also related to PCD [82], and there is a relationship between motile cilia and spine morphology [83]. Additional disorders of the skeletal system, which includes bone and connective tissue, are also produced by mutations in primary cilia genes [84] and are frequently associated with respiratory infections and bronchiectasis. Osteoporosis, which may appear when ciliary genes, such as IFT80, IFT88, or Kif3a, are mutated [84], is considered a risk factor for bronchiectasis [85,86].…”

“…Additional disorders of the skeletal system, which includes bone and connective tissue, are also produced by mutations in primary cilia genes [84] and are frequently associated with respiratory infections and bronchiectasis. Osteoporosis, which may appear when ciliary genes, such as IFT80, IFT88, or Kif3a, are mutated [84], is considered a risk factor for bronchiectasis [85,86]. Asphyxiating thoracic dystrophy (Jeune's syndrome) may be caused by mutations in ciliary genes such as DYNC2H1 [75], and mutations in DYNC2H1 [87] and in KIAA0753 [88] were present in patients with recurrent respiratory infections.…”

Microtubule‐associated proteins and enzymes modifying tubulin

“…Recent research suggests that mechanical forces are additional factors that impact the functions of MTs (X. Li et al, 2022;Seetharaman et al, 2022).…”

“…Small molecules that act on MTs, MAPs, and the enzymes also influence the functions of MTs (Warner, Li, & Li, 2022). Recent research suggests that mechanical forces are additional factors that impact the functions of MTs (X. Li et al, 2022; Seetharaman et al, 2022).…”