Primary cilia: Versatile regulator in cartilage development

Abstract

Cartilage is a connective tissue in the skeletal system and has limited regeneration ability and unique biomechanical reactivity. The growth and development of cartilage can be affected by different physical, chemical and biological factors, such as mechanical stress, inflammation, osmotic pressure, hypoxia and signalling transduction. Primary cilia are multifunctional sensory organelles that regulate diverse signalling transduction and cell activities. They are crucial for the regulation of cartilage development and act in a variety of ways, such as react to mechanical stress, mediate signalling transduction, regulate cartilage‐related diseases progression and affect cartilage tumorigenesis. Therefore, research on primary cilia‐mediated cartilage growth and development is currently extremely popular. This review outlines the role of primary cilia in cartilage development in recent years and elaborates on the potential regulatory mechanisms from different aspects.

Predictors of Spontaneous Remodelling of Angular Knee Deformities in Children with Healed Nutritional Rickets: A Prospective Cohort Study Protocol

“…There is recognizable basic science knowledge to suggest that mechanical loading of the growth plate has a significant impact on chondrocyte proliferation and hypertrophy and subsequent skeletal genesis [29][30][31][32]. These inferences apply to both physiologic and pathologic mechanical stresses.…”

Physiological and Pathophysiological Aspects of Primary Cilia—A Literature Review with View on Functional and Structural Relationships in Cartilage

“…In addition, these experiments affected the collagenase MMP-13 (=matrix metalloproteinase 13 also known as collagenase-3) levels [62]. MMP-13 is a key protein for the cartilage matrix catabolism [63]. It is responsible for chondrocyte proliferation, cellular migration, cell apoptosis, degradation of collagen II, alterations of the ECM and the cartilage to bone transformation [64].…”

“…Thompson et al discovered that the expression of MMP-13 and ADAMTS-5 is neither dependent of Ihh nor in coexistence with IL-1β [97]. However, Tao et al showed disturbed ciliary function via knock out of the ciliary motor protein Kif3a in mice leads to altered MMP-13 levels [63]. He et al described another PC-associated signaling pathway that leads to increased MMP-13 and MMP-1 levels.…”

The Primary Cilium on Cells of Developing Skeletal Rudiments; Distribution, Characteristics and Response to Mechanical Stimulation

“…The primary cilium is a non-motile, microtubule-supported organelle that often projects outward from the cell surface, allowing sensation of the mechanical environment ( Singla and Reiter, 2006 ; Malone et al, 2007 ; Deren et al, 2016 ; Spasic and Jacobs, 2017b ). It is present on diverse cell types in developing and mature tissues and has been studied during organogenesis of the kidneys, nervous system, heart, and skeleton (reviewed in Gerdes et al, 2009 ; Fry et al, 2014 ; Tao et al, 2020 ). The membrane encapsulating the cilium axoneme is distinct from the adjacent cellular membrane, with localized membrane-bound receptors and other cilium-specific proteins (reviewed in Jensen and Leroux, 2017 ).…”

“…Cilia are vital to correct Hh signaling in the limb buds of mouse and chick embryos, leading to misspecification of digits and polydactyly when cilia are absent or non-functional ( Bangs et al, 2011 ). The absence of cilia from mesenchymal condensations (under Dermo1-Cre) or cartilage (Col2aI-Cre), or global mutations of ciliary genes, result in limb shortening, disorganized chondrocytes, craniofacial abnormalities, hypomineralization, and dwarfism, suggesting altered cell signaling that impacts skeletal differentiation ( Koyama et al, 2007 ; Song et al, 2007 ; Tao et al, 2020 ). Yuan and Yang (2015) showed that primary chondrocytes derived from postnatal cilia-deficient mice had deficient Hh signaling and enhanced responsiveness to canonical Wnt signals.…”