The evolving therapeutic landscape of genetic skeletal disorders

Sabir, Ataf; Cole, Trevor

doi:10.1186/s13023-019-1222-2

Cited by 24 publications

(27 citation statements)

References 84 publications

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“…The results provided new ideas and directions for the research on the occurrence and development of osteoporosis. Bone metabolic diseases include osteoporosis, end secretory bone disease, renal bone disease, hereditary bone disease and so on, among which osteoporosis is the most common disease [30,31]. Nowadays, with the rapid acceleration of aging, the incidence of osteoporosis is on the rise.…”

Section: Discussionmentioning

confidence: 99%

Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice

Xue¹,

Hu²,

Chen³

et al. 2022

Int. J. Biol. Sci.

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Irisin is well-known to contribute to bone homeostasis due to its bidirectional regulation on osteogenesis and osteoclastogenesis. However, the mechanisms of irisin involved in mesenchymal stem/stromal cells (MSCs)-derived osteogenesis are still under investigated. Fibronectin type III domain-containing protein 5 (FNDC5) is the precursor protein of irisin, compare with wild type (WT) littermates, FNDC5 -/-mice lost bone mass significantly, collectively evidenced by the decrease of bone mineral density (BMD), impaired bone formation and reduced N-terminal propertied of type I procollagen (P1NP) in sera. Meanwhile, the bone resorbing of FNDC5 -/-mice has enhanced accompanied by increased tartrate phosphatase (TRAP) staining cells morphologically and cross-Linked C-telopeptide of type 1 collagen (CTX) level in sera. In vitro study showed that lack of irisin impeded the MSC-derived osteogenesis of FNDC5 -/-mice. The addition of irisin promote the osteogenesis of WT and irisin-deficient MSCs, by activating αV integrin-induced ERK/STAT pathway, subsequently enhancing bone morphogenetic protein 2 (BMP2) expression and BMP/SMAD signaling activation. Taken together, these findings further indicate that irisin regulates bone homeostasis. Moreover, irisin promotes MSC-derived osteogenesis by binding to αV integrin and activating BMP/SMAD signaling consequently. Thus, irisin may be a promising therapeutic target for osteoporosis and bone defects.

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Section: Discussionmentioning

confidence: 99%

Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice

Xue¹,

Hu²,

Chen³

et al. 2022

Int. J. Biol. Sci.

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“…Additionally, as shown in the study published in 2012, patients with HME present a lower Health-Related Quality of Life factor in comparison with the control group (Chhina et al, 2012). For these reasons and because of everyday life discomfort experienced by many patients, new potential treatments need to be investigated (Sabir and Cole, 2019).…”

Section: Treatment and Novel Therapeutic Strategiesmentioning

confidence: 99%

Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies

et al. 2021

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Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized by multiple benign cartilage-capped bony outgrowths, termed exostoses or osteochondromas, that locate most commonly in the juxta-epiphyseal portions of long bones. Affected individuals usually complain of persistent pain caused by the pressure on neighboring tissues, disturbance of blood circulation, or rarely by spinal cord compression. However, the most severe complication of this condition is malignant transformation into chondrosarcoma, occurring in up to 3.9% of HMEs patients. The disease results mainly from heterozygous loss-of-function alterations in the EXT1 or EXT2 genes, encoding Golgi-associated glycosyltransferases, responsible for heparan sulfate biosynthesis. Some of the patients with HMEs do not carry pathogenic variants in those genes, hence the presence of somatic mutations, deep intronic variants, or another genes/loci is suggested. This review presents the systematic analysis of current cellular and molecular concepts of HMEs along with clinical characteristics, clinical and molecular diagnostic methods, differential diagnosis, and potential treatment options.

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“…This should improve access to high-quality healthcare for patients and their families and should facilitate the generation of reliable data on rare skeletal disorders in order to improve further treatment strategies [9,15]. In recent years, specific treatments have been developed for a small number of skeletal disorders [9,16], but for the majority of skeletal disorders current treatment options consists of symptomatic approaches and in monitoring for treatable complications [2,9]. Skeletal disorders are associated with a highly variable range of clinical and nonclinical challenges for patients, families and health care providers and therefore need a multidisciplinary management approach [2,9,17].…”

Section: Multidisciplinary Management Approachmentioning

confidence: 99%

Rare skeletal disorders: a multidisciplinary postnatal approach to diagnosis and management

Walleczek

Förster

Seyr

et al. 2021

Wien Med Wochenschr

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SummarySkeletal disorders are inherited disorders with significant skeletal involvement and most of them are rare or extremely rare. Based on the clinical, radiological and genetic phenotype, the group of skeletal disorder comprises more than 450 different and highly heterogeneous disorders. In skeletal disorders rapid and precise diagnoses are urgently needed for patient care and are based on the combination of clinical, radiological and genetic analysis. Novel genetic techniques have revolutionized diagnostics and have a huge impact on counseling of patients and families. Disease-specific long-term management in a multidisciplinary healthcare team in highly specialized centers is recommended to optimize care for these patients. Here we describe a multidisciplinary postnatal approach for the diagnosis and management of patients and families with rare skeletal disorders at the Vienna Bone and Growth Center. We discuss the value of a multidisciplinary diagnostic and management approach in the postnatal setting and provide a diagnostic flowchart for rare skeletal disorders.

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The evolving therapeutic landscape of genetic skeletal disorders

Cited by 24 publications

References 84 publications

Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice

Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice

Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies

Rare skeletal disorders: a multidisciplinary postnatal approach to diagnosis and management

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