Lessons from joint development for cartilage repair in the clinic

Thorup, Anne-Sophie; Dell’Accio, Francesco; Eldridge, S.

doi:10.1002/dvdy.228

Cited by 6 publications

(9 citation statements)

References 171 publications

(422 reference statements)

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“…These intrinsic differences may not only influence embryonic patterning of skeletal elements but also postnatal growth and regeneration mechanisms. For example, developmental molecular programs are reactivated postnatally during repair of articular cartilage and calvarial bones 121,122 . Additionally, embryonic Hox gene expression patterns can be maintained within stem cell populations postnatally where they influence stem cell characteristics 69,123 .…”

Section: Introductionmentioning

confidence: 99%

Making and shaping endochondral and intramembranous bones

Galea

Zein

Allen

et al. 2020

Developmental Dynamics

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Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load‐bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair.

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Section: Introductionmentioning

confidence: 99%

Making and shaping endochondral and intramembranous bones

Galea

Zein

Allen

et al. 2020

Developmental Dynamics

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“…Consistent with the in vivo study, strategies to inhibit hypertrophic maturation of chondrocytes and enhance the synthesis of ECM represent potential new therapeutic modalities, an excellent chondro-protective effect had been approved in vitro studies. The chondrocytes are responsible for the maintenance of the articular cartilage [ 37 ], which would provide a valid strategy for the prevention and treatment of KOA [ 38 ]. Previous investigations implied that PTH (1–34) could enhance the proliferation of chondrocytes [ 39 ], which was replenished in our current study.…”

Section: Discussionmentioning

confidence: 99%

Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice

Liu

Chen

et al. 2023

Journal of Orthopaedic Translation

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“…Subsequently, chondrocytes in the central part of the skeletal elements (diaphysis) become hypertrophic—expressing collagen type X and other markers—and are eventually replaced by bone. This process, called endochondral bone formation, spares the last few layers of cells proximal to the joint which are resistant to hypertrophic differentiation, vascular invasion, calcification and bone formation and give rise to the permanent articular cartilage (Thorup et al , 2020a ). During osteoarthritis, however, ectopic and pathological chondrocyte hypertrophy and calcification take place within the articular cartilage and drive its breakdown (Saito et al , 2010 ; Yang et al , 2010 ; Bertrand et al , 2011 , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Disease modification and symptom relief in osteoarthritis using a mutated GCP ‐2/ CXCL6 chemokine

et al. 2022

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We showed that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is essential for cartilage homeostasis. Here we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP-2) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP-2 expression was retained in adult articular cartilage. GCP-2 loss-of-function inhibited extracellular matrix production. GCP-2 treatment promoted chondrogenesis in vitro and in human cartilage organoids implanted in nude mice in vivo. To exploit the chondrogenic activity of GCP-2, we disrupted its chemotactic activity, by mutagenizing a glycosaminoglycan binding sequence, which we hypothesized to be required for the formation of a GCP-2 haptotactic gradient on endothelia. This mutated version (GCP-2-T) had reduced capacity to induce transendothelial migration in vitro and in vivo, without affecting downstream receptor signaling through AKT, and chondrogenic activity. Intra-articular adenoviral overexpression of GCP-2-T, but not wild type GCP-2, reduced pain and cartilage loss in instability-induced osteoarthritis in mice. We suggest that GCP-2-T may be used for disease modification in osteoarthritis.

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Lessons from joint development for cartilage repair in the clinic

Cited by 6 publications

References 171 publications

Making and shaping endochondral and intramembranous bones

Making and shaping endochondral and intramembranous bones

Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice

Disease modification and symptom relief in osteoarthritis using a mutated GCP ‐2/ CXCL6 chemokine

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