Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine

Abstract

Amputation injuries in mammals are typically non-regenerative, however joint regeneration is stimulated by BMP9 treatment (Yu et al., 2019) indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9 treated cells results in differentiation of hyaline cartilage and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9 responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establishes a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine.

How the Hyaline Cartilage is Formed in the Siphonopoda as the Model of Higher Organisms?

“…The third stage during which a dense condensation takes place to form a disc of unknown structure is the collecting of collagen filaments inside the first step. Yu et al, 2022). The stages of formation in the cephalopods resemble the origin of bone in semi-invertebrates and vertebrates because the Octopus vulgaris is considered an advanced and higher invertebrate (Liu, 2019;Liu et al, 2021;Allen et al, 2022).…”

“…The hyaline cartilage began to appear in phylum Annelida as a solid capsule, originating from solid epidermal connective tissue, and in echinoderms by lower condensation of collagen fibers, and then differentiated into cephalopod for different types and functions (Bairati et al, 1998;Cole et al, 2004;Whittaker et al, 2006;Brittberg et al, 2008;Cole, 2011;Person, 2012;Owen, 2022). The cephalopods contain different types of hyaline cartilage according to the differentiation and functions of fibroblast cell itself; in addition, they differ from other invertebrates with respect to the formation from lose tissue and the nature of origin from connective tissue (Boyan et al, 1999;Cole et al, 2004a;Hall, 2005;Cole, 2011a;Ehrlich, 2015;Grässel et al, 2016;Irawan et al, 2018;Krings et al, 2022;Ragheb et al, 2022;Yu, 2022). The differential process first appears and condensation in crustaceans passes to top qualification in Mollusca as the first appearance of the cartilage in several tissues of the animal body parts as mantle tissue.…”

Advances in the role and mechanism of fibroblasts in fracture healing

“…Yu et al. ( 77 ) found that BMP-9 could induce fibroblasts to differentiate into hyaline cartilage, and then carried out in vivo experiments to implant hyaline cartilage into acutely damaged joints. It was found that the transplanted hyaline cartilage survived and maintained the hyaline cartilage phenotype after implantation, but did not form mature articular cartilage.…”

Latest Advances in Chondrocyte-Based Cartilage Repair

“…The specific p38 MAPK plays multiple roles in chondrocyte differentiation [ 91 , 92 , 93 ]. It is considered an active regulator in chondrocyte differentiation, as well as chondrogenesis [ 90 ], due to its positive regulation of differentiation of prechondrogenic limb into hyaline chondrocytes which produce hyaline cartilage, the most widespread cartilage that is usually present within joints [ 94 ]. All of the positive influences FGF19 has on cartilage by increasing mitochondrial biogenesis and promoting chondrogenesis provide greater insight into the impacts FGF19 has on chondrocytes and cartilage.…”