Research progress on the hedgehog signalling pathway in regulating bone formation and homeostasis

Zhou, Huan; Zhang, Lei; Chen, Yue; C, Zhu; Chen, Fa‐Ming; Li, Ang

doi:10.1111/cpr.13162

Cited by 34 publications

(23 citation statements)

References 92 publications

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“…Ihh inhibits MSC differentiation to adipocytes and promotes differentiation to osteoblasts. Ihh signaling also acts synergistically with the Wnt and BMP pathways to promote bone formation ( 65 ). Shh upregulates osterix, an osteoblast-specific transcription factor that induces gene expression, which promotes differentiation of preosteoblasts to mature osteoblasts ( 66 , 67 ).…”

Section: Stimulation Of Bone Formationmentioning

confidence: 99%

Impact of the host response and osteoblast lineage cells on periodontal disease

Zhou

Graves²

2022

Front. Immunol.

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Periodontitis involves the loss of connective tissue attachment and alveolar bone. Single cell RNA-seq experiments have provided new insight into how resident cells and infiltrating immune cells function in response to bacterial challenge in periodontal tissues. Periodontal disease is induced by a combined innate and adaptive immune response to bacterial dysbiosis that is initiated by resident cells including epithelial cells and fibroblasts, which recruit immune cells. Chemokines and cytokines stimulate recruitment of osteoclast precursors and osteoclastogenesis in response to TNF, IL-1β, IL-6, IL-17, RANKL and other factors. Inflammation also suppresses coupled bone formation to limit repair of osteolytic lesions. Bone lining cells, osteocytes and periodontal ligament cells play a key role in both processes. The periodontal ligament contains cells that exhibit similarities to tendon cells, osteoblast-lineage cells and mesenchymal stem cells. Bone lining cells consisting of mesenchymal stem cells, osteoprogenitors and osteoblasts are influenced by osteocytes and stimulate formation of osteoclast precursors through MCSF and RANKL, which directly induce osteoclastogenesis. Following bone resorption, factors are released from resorbed bone matrix and by osteoclasts and osteal macrophages that recruit osteoblast precursors to the resorbed bone surface. Osteoblast differentiation and coupled bone formation are regulated by multiple signaling pathways including Wnt, Notch, FGF, IGF-1, BMP, and Hedgehog pathways. Diabetes, cigarette smoking and aging enhance the pathologic processes to increase bone resorption and inhibit coupled bone formation to accelerate bone loss. Other bone pathologies such as rheumatoid arthritis, post-menopausal osteoporosis and bone unloading/disuse also affect osteoblast lineage cells and participate in formation of osteolytic lesions by promoting bone resorption and inhibiting coupled bone formation. Thus, periodontitis involves the activation of an inflammatory response that involves a large number of cells to stimulate bone resorption and limit osseous repair processes.

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Section: Stimulation Of Bone Formationmentioning

confidence: 99%

Impact of the host response and osteoblast lineage cells on periodontal disease

Zhou

Graves²

2022

Front. Immunol.

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“…RAB23, a suppressor of Hh signalling was found to inhibit GLI function through interaction with SUFU, another negative regulator of Hh signalling. In the absence of Hh ligands, GLI is converted to repressor form, thus preventing signal transduction [ 41 , 42 ]. However, the SHH non-canonical signalling cascade, which is GLI-independent, could occur via SMO-dependent or independent route [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles of Human Mesenchymal Stromal Cells Derived from Wharton’s Jelly and Amniotic Membrane before and after Osteo-Induction Using NanoString Platform

Hiew

Akhir

Teoh

2022

CIMB

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The use of perinatal mesenchymal stem cells (MSCs) in bone tissue regeneration and engineering to substitute bone marrow MSCs has drawn great interest due to their high yield, ease of procurement, multilineage differentiation potential and lack of ethical concerns. Although amniotic membrane (AM) and Wharton’s jelly (WJ)-derived MSCs have been widely shown to possess osteogenic differentiation potential, the intrinsic properties determining their osteogenic capacity remain unclear. Here, we compared gene expression profiles of AM- and WJ-MSCs at basal and osteogenic conditions by using the NanoString Stem Cell Panel containing regulatory genes associated with stemness, self-renewal, Wnt, Notch and Hedgehog signalling pathways. At basal condition, WJ-MSCs displayed higher expression in most genes regardless of their functional roles in self-renewal, adhesion, or differentiation signalling pathways. After osteo-induction, elevated expression of self-renewal genes ADAR and PAFAH1B1 was observed in AM-MSCs, while stemness genes MME and ALDH1A1 were upregulated in WJ-MSC. Both MSCs showed differences in genes associated with ligands, receptors and ubiquitin ligases of the Notch pathway. In addition, further evidence was demonstrated in some signalling molecules including CTBPs, protein kinases, phosphatases, RHOA, RAC1. Downstream targets HES1 and JUN especially showed higher expression in non-induced WJ-MSCs. Hedgehog genes initially expressed in both MSCs were downregulated in WJ-MSCs during osteogenesis. This study has provided insights into the intrinsic biological differences that may lead to their discrimination in therapeutic intervention.

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“…miR-1 is lowly expressed in human OA joint tissues, and overexpression of it inhibits the development of OA by inhibiting Ihh signaling ( 85 ). The activation of Hh signaling plays an important role in the occurrence and development of OA, and a large number of studies have proved that targeting and blocking this pathway can treat OA ( 97 , 98 ), laying a certain foundation for its future clinical translation.…”

Section: Treatment Of Rheumatic Diseases By Targeting the Hh Signalin...mentioning

confidence: 99%

Role of the hedgehog signaling pathway in rheumatic diseases: An overview

Xing

Kang

et al. 2022

Front. Immunol.

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Hedgehog (Hh) signaling pathway is an evolutionarily conserved signal transduction pathway that plays an important regulatory role during embryonic development, cell proliferation, and differentiation of vertebrates, and it is often inhibited in adult tissues. Recent evidence has shown that Hh signaling also plays a key role in rheumatic diseases, as alterations in their number or function have been identified in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic sclerosis, and Sjogren’s Syndrome. As a result, emerging studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of Hh signaling in rheumatic diseases.

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Research progress on the hedgehog signalling pathway in regulating bone formation and homeostasis

Cited by 34 publications

References 92 publications

Impact of the host response and osteoblast lineage cells on periodontal disease

Impact of the host response and osteoblast lineage cells on periodontal disease

Gene Expression Profiles of Human Mesenchymal Stromal Cells Derived from Wharton’s Jelly and Amniotic Membrane before and after Osteo-Induction Using NanoString Platform

Role of the hedgehog signaling pathway in rheumatic diseases: An overview

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