Fibroblast Growth Factor Receptor 3 Inhibits Osteoarthritis Progression in the Knee Joints of Adult Mice

Tang, Junzhou; Su, Nan; Zhou, Siru; Xie, Yangli; Huang, Junlan; Wen, Xuan; Wang, Zuqiang; Wang, Quan; Xu, Wei; Du, Xiaolan; Chen, Hangang; Chen, Lin

doi:10.1002/art.39739

Cited by 68 publications

(50 citation statements)

References 57 publications

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“…Interestingly, recent studies on mice have indicated that the FGFR3-mutation might protect from the development of arthritis in achondroplasia. 59 Two studies reported on osteopenia in achondroplasia, 17,19 but the studies are small and the findings need to be confirmed in future studies.…”

Section: Medical Complications Health Characteristics and Psychosomentioning

confidence: 97%

Current knowledge of medical complications in adults with achondroplasia: A scoping review

et al. 2019

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This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice. K E Y W O R D S achondroplasia, adults, health-related quality of life, health status, medical complications, review

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Section: Medical Complications Health Characteristics and Psychosomentioning

confidence: 97%

Current knowledge of medical complications in adults with achondroplasia: A scoping review

et al. 2019

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“…Sh3bp4 thus represents a new osteoarthritis susceptibility gene, the deletion of which accelerates joint damage. Its role in disease pathogenesis may involve the key TfR, FGFR, mTOR and Wnt signalling pathways, which regulate bone and cartilage homeostasis and tissue repair [47][48][49][50] .…”

Section: Early Onset Osteoarthritis In Bhlhe40 -/And Sh3pb4 -/Mutant mentioning

confidence: 99%

Accelerating functional gene discovery in osteoarthritis

Butterfield

Curry

Steinberg

et al. 2019

Preprint

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Osteoarthritis causes debilitating pain and disability, resulting in a huge socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in unselected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models. We demonstrate sensitivity of the methods by identifying age-related degenerative joint damage in wild-type mice. Finally, we generate mutant mice with an osteoarthritis-associated polymorphism in the Dio2 gene by Crispr/Cas9 genome editing and demonstrate a protective role in disease onset with public health implications. This expanding resource of unselected mutant mice will transform the field by accelerating functional gene discovery in osteoarthritis and offering unanticipated drug discovery opportunities for this common and incapacitating chronic disease.

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“…Valverde‐Franco et al showed that the absence of FGFR3 signaling in the joints of Fgfr3 −/− mice led to premature cartilage degeneration and early arthritis. Recently, Tang et al indicated that adult mice carrying conditional Fgfr3 deletion in chondrocytes caused aggravated cartilage degeneration after OA‐induced surgery. Conversely, chondrocyte‐specific Fgfr3 activation ameliorated cartilage degeneration via downregulation of Indian hedgehog signaling in articular chondrocytes …”

mentioning

confidence: 99%

Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia

Okura

Matsushita

Mishima

et al. 2017

Journal Orthopaedic Research

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The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3 ach ) carrying a heterozygous gain-of-function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild-type mice, and Fgfr3 ach mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro-computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild-type mice and Fgfr3 ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild-type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3 ach mice than in wild-type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3 ach mice, and the Sb.Th med was significantly larger in wild-type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3 ach mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. ß

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Fibroblast Growth Factor Receptor 3 Inhibits Osteoarthritis Progression in the Knee Joints of Adult Mice

Abstract: Our findings indicate that FGFR-3 delays OA progression in mouse knee joints at least in part via down-regulation of IHH signaling in articular chondrocytes.

Cited by 68 publications

References 57 publications

Current knowledge of medical complications in adults with achondroplasia: A scoping review

Current knowledge of medical complications in adults with achondroplasia: A scoping review

Accelerating functional gene discovery in osteoarthritis

Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia

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