Bone morphogenetic proteins in the development and healing of synovial joints*,**,★
Section snippets
Methods
A review of the published literature using a search of the entire PubMed database made available by the National Library of Medicine was undertaken. The search included articles from 1966 to 2000. Key articles on joint development and BMPs/GDFs were identified, and additional articles of interest were selected from the bibliographies of published literature.
Animal models and human disease
There are a number of syndromes characterized by abnormalities of synovial joints, and recently the gene mutations responsible for a number of these have been identified (Table 1).BMP Disease Gene Abnormality Phenotype Reference No. Mouse GDF-5 Brachypodism Frame shift Short limbs, loss of PIPs, wrist and ankle fusions 15, 16 BMP-5 Short ear mouse Deletion Short ears; small, long bones (79) Human GDF-5
Discussion
Joint formation appears to depend on localized and stage-dependent activities of BMPs. In addition, it also depends on surrounding tissues such as the muscles, which themselves may induce changes in gene expression in the developing joint by mechanical stimulation. The expression of BMP antagonists is likely to be a key determinant during joint development suggesting that down-regulation/ablation of BMP activity including GDF-5 is essential for joint development. The actions of BMPs in animal
Acknowledgements
We thank Paul Buxton for providing the radioactive in situ hybridization data, Vicki Church for critically reading the manuscript, and Frank Luyten and Tom Jessel for providing the GDF-5 and chordin complementary DNA probes, respectively.
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Cited by (60)
Association of synovial expression of growth and differentiation factor 5 (GDF5) with radiographic severity of knee osteoarthritis
2022, HeliyonCitation Excerpt :This pathway is involved in the transcription of proteins involved in extracellular matrix synthesis, including COL2A1 and ACAN. GDF5 plays a major role in synovial joint formation and articular cartilage synthesis [15]. Several studies support a role of GDF5 in skeletal development.
MicroRNA-449a upregulation promotes chondrocyte extracellular matrix degradation in osteoarthritis
2018, Biomedicine and PharmacotherapyCitation Excerpt :These data suggest that miR-449a may have a destructive effect on OA progression via its ability to promote ECM degradation. GDF5 is one of the earliest markers of joint formation, and is involved in the maintenance and repair of cartilage [30,31]. Both in vitro and in vivo studies have confirmed the key role of GDF5 in the occurrence and development of OA.
Intra-articular therapy with recombinant human GDF5 arrests disease progression and stimulates cartilage repair in the rat medial meniscus transection (MMT) model of osteoarthritis
2017, Osteoarthritis and CartilageCitation Excerpt :Growth and differentiation factor-5 (GDF5) is a bone morphogenic protein (also known as BMP-14 and CDMP-1) and a member of the transforming growth factor-β (TGF-β) superfamily1. GDF5 is a developmental marker for early joint formation in the embryo, and is involved in the maintenance and repair of bone and cartilage in the adult2,3. The importance of GDF5 in synovial joint development is well established2, as is the importance of GDF5 for normal synovial joint function4.
Structure and Function
2015, Textbook of Pediatric RheumatologyBiology of the Normal Joint
2012, Kelley's Textbook of Rheumatology: Volume 1-2, Ninth EditionRheumatoid Arthritis Recapitulates Events Relevant in Blastocyst Implantation and Embryogenesis: A Pathogenetic Theory
2011, Seminars in Arthritis and RheumatismCitation Excerpt :Loss-of-function mutations of GDF5 lead to Hunter—Thompson-type chondrodysplasia, Grebe-type chondrodysplasia, fibular hypoplasia with complex brachydactyly, or proximal symphalangism (loss of the proximal interphalangeal joints due to complete ankylosis). Thus, GDF5 is an important factor for regular joint development (71). GDF5 is expressed in synovial fibroblasts of normal subjects and patients with RA/OA (72).
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Christopher J. Edwards, MRCP: Lecturer in Rheumatology, The Kennedy Institute of Rheumatology, Imperial College School of Medicine, London, UK; Philippa H. Francis-West, PhD: Reader in Developmental Biology, Department of Craniofacial Development, Kings College London, London, England.
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Supported by the Arthritis Research Campaign.
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Address reprint requests to Dr Christopher Edwards, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. E-mail: [email protected]