scholarly journals Correction: H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rui Shao ◽  
Zhong Zhang ◽  
Zhan Xu ◽  
Huiling Ouyang ◽  
Lijun Wang ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Fracture Repair ◽  
Chondrocyte Differentiation

scholarly journals H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rui Shao ◽  
Zhong Zhang ◽  
Zhan Xu ◽  
Huiling Ouyang ◽  
Lijun Wang ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Chondrogenic Differentiation ◽  
Transcriptional Control ◽  
Bone Development ◽  
Skeletal Development ◽  
Hypoxia Inducible Factor ◽  
Fracture Repair ◽  
Skeletal Growth ◽  
Long Bone ◽  
Chondrocyte Differentiation

AbstractChondrocyte differentiation is a critical process for endochondral ossification, which is responsible for long bone development and fracture repair. Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation; however, epigenetic regulation of chondrocyte differentiation remains to be further studied. NSD1 is a H3K36 (histone H3 at lysine 36) methyltransferase. Here, we showed that mice with Nsd1 deficiency in Prx1+ mesenchymal progenitors but not in Col2+ chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation. Via combined RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we identified sex determining region Y box 9 (Sox9), the key transcription factor of chondrogenic differentiation, as a functional target gene of NSD1. Mechanistically, NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region, constituting a novel epigenetic regulatory mechanism of chondrogenesis. Moreover, we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α (HIF1α), which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression. Collectively, the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation, skeletal growth, and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.

scholarly journals Microarray Analyses of Gene Expression during Chondrocyte Differentiation Identifies Novel Regulators of Hypertrophy

2005 ◽  
Vol 16 (11) ◽  
pp. 5316-5333 ◽  
Author(s):  
Claudine G. James ◽  
C. Thomas G. Appleton ◽  
Veronica Ulici ◽  
T. Michael Underhill ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Bone Development ◽  
Skeletal Development ◽  
Expression Patterns ◽  
Chondrocyte Differentiation ◽  
Endochondral Bone ◽  
Temporal Gene Expression ◽  
Affymetrix Microarrays ◽  
Time Period ◽  
And Cluster Analysis

Ordered chondrocyte differentiation and maturation is required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. We used Affymetrix microarrays to examine temporal gene expression patterns during chondrogenic differentiation in a mouse micromass culture system. Robust normalization of the data identified 3300 differentially expressed probe sets, which corresponds to 1772, 481, and 249 probe sets exhibiting minimum 2-, 5-, and 10-fold changes over the time period, respectively. GeneOntology annotations for molecular function show changes in the expression of molecules involved in transcriptional regulation and signal transduction among others. The expression of identified markers was confirmed by RT-PCR, and cluster analysis revealed groups of coexpressed transcripts. One gene that was up-regulated at later stages of chondrocyte differentiation was Rgs2. Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation, thus providing functional validation of microarray data. Collectively, these analyses provide novel information on the temporal expression of molecules regulating endochondral bone development.

scholarly journals Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 332 ◽  
Author(s):  
Jennifer T. Zieba ◽  
Yi-Ting Chen ◽  
Brendan H. Lee ◽  
Yangjin Bae
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Human Genetics ◽  
Skeletal Development ◽  
Gene Activation ◽  
Fracture Repair ◽  
Loss Of Function ◽  
Age Related ◽  
Complex Process ◽  
And Cartilage

Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases.

Syndecan 4 supports bone fracture repair, but not fetal skeletal development, in mice

2013 ◽  
Vol 65 (3) ◽  
pp. 743-752 ◽  
Author(s):  
Jessica Bertrand ◽  
Richard Stange ◽  
Heriburg Hidding ◽  
Frank Echtermeyer ◽  
Giovanna Nalesso ◽  
...  
Keyword(s):  
Bone Fracture ◽  
Skeletal Development ◽  
Fracture Repair

Use of high-dose oral bisphosphonate therapy for symptomatic fibrous dysplasia of the skull

2008 ◽  
Vol 109 (5) ◽  
pp. 889-892 ◽  
Author(s):  
Kevin Chao ◽  
Laurence Katznelson
Keyword(s):  
Fibrous Dysplasia ◽  
Therapeutic Option ◽  
Skeletal Development ◽  
Bisphosphonate Therapy ◽  
Fracture Repair ◽  
High Dose ◽  
Oral Bisphosphonate ◽  
Dose Oral ◽  
Insight Into

Fibrous dysplasia of the bone in adults is a rare anomaly of skeletal development caused by a defect in differentiation of osteoblasts. This condition is associated with bone pain, bone deformity, and an increased incidence of fracture. Involvement of the skull is associated with headache along with dysmorphic features. Until recently, the principal treatment has been resection or fracture repair, although the latter is often palliative at best. However, new insight into the molecular mechanism of fibrous dysplasia has led to the use of bisphosphonates to treat this disease. The authors examined the effects of high-dose oral alendronate (40 mg daily) for 6 months on 3 adult patients with intractable headache due to fibrous dysplasia of the skull. Each patient had disease processes not amenable to surgery. The patients underwent clinical follow-up at 1, 3, and 6 months. Their pain levels were documented at each visit by using a visual analog scale. All 3 patients demonstrated a significant decrease in pain levels and became independent of scheduled analgesics. Tumor bulk did not progress during this interval in any patient. Overall, alendronate was tolerated well, although in 1 patient it was discontinued early due to esophagitis. High-dose oral bisphosphonate therapy is an alternative therapeutic option for the palliative treatment of patients with fibrous dysplasia of the skull.

scholarly journals 40 YEARS OF IGF1: Role of IGF1 and EFN–EPH signaling in skeletal metabolism

2018 ◽  
Vol 61 (1) ◽  
pp. T87-T102 ◽  
Author(s):  
Richard C Lindsey ◽  
Charles H Rundle ◽  
Subburaman Mohan
Keyword(s):  
Signaling Pathways ◽  
Bone Growth ◽  
Cell Function ◽  
Skeletal Development ◽  
Cell Types ◽  
Bone Cell ◽  
Fracture Repair ◽  
Development And Differentiation ◽  
Major Mediator

Insulin-like growth factor 1(IGF1) and ephrin ligand (EFN)–receptor (EPH) signaling are both crucial for bone cell function and skeletal development and maintenance. IGF1 signaling is the major mediator of growth hormone-induced bone growth, but a host of different signals and factors regulate IGF1 signaling at the systemic and local levels. Disruption of the Igf1 gene results in reduced peak bone mass in both experimental animal models and humans. Additionally, EFN–EPH signaling is a complex system which, particularly through cell–cell interactions, contributes to the development and differentiation of many bone cell types. Recent evidence has demonstrated several ways in which the IGF1 and EFN–EPH signaling pathways interact with and depend upon each other to regulate bone cell function. While much remains to be elucidated, the interaction between these two signaling pathways opens a vast array of new opportunities for investigation into the mechanisms of and potential therapies for skeletal conditions such as osteoporosis and fracture repair.

scholarly journals Syndecan-4 is critically involved in inflammatory driven bone fracture repair, but not fetal skeletal development

2012 ◽  
Vol 20 ◽  
pp. S25-S26
Author(s):  
J. Bertrand ◽  
R. Stange ◽  
H. Hidding ◽  
F. Echtermeyer ◽  
G. Nalesso ◽  
...  
Keyword(s):  
Bone Fracture ◽  
Skeletal Development ◽  
Fracture Repair

scholarly journals WISP-1 Is an Osteoblastic Regulator Expressed During Skeletal Development and Fracture Repair

2004 ◽  
Vol 165 (3) ◽  
pp. 855-867 ◽  
Author(s):  
Dorothy M. French ◽  
Raji J. Kaul ◽  
Aloma L. D'souza ◽  
Craig W. Crowley ◽  
Min Bao ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Fracture Repair

Basic fibroblast growth factor destabilizes osteonectin mRNA in osteoblasts

1998 ◽  
Vol 274 (3) ◽  
pp. C734-C740 ◽  
Author(s):  
Anne M. Delany ◽  
Ernesto Canalis
Keyword(s):  
Extracellular Matrix ◽  
Skeletal Development ◽  
Fracture Repair ◽  
Osteoblastic Cell ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Osteoblastic Cell Line ◽  
The Stability

Osteonectin (secreted protein acidic and rich in cysteine, 40-kDa basement membrane) is a glycoprotein abundantly expressed in bone and in other tissues undergoing active remodeling. Fibroblast growth factors (FGFs) are important in skeletal development and fracture repair, events associated with extracellular matrix remodeling. We used the murine osteoblastic cell line MC3T3 to determine whether basic FGF (bFGF) regulates osteonectin expression in bone. Northern blot analysis showed that bFGF decreased osteonectin transcripts in a dose- and time-dependent manner. This regulation was independent of the mitogenic effect of bFGF but was dependent on new protein synthesis. Immunoprecipitation of [35S]methionine-cysteine osteoblast-conditioned medium and cell layer proteins showed that bFGF decreased osteonectin synthesis. Nuclear runoff assays failed to reveal regulation of osteonectin gene transcription by bFGF. However, bFGF dramatically decreased the stability of osteonectin mRNA in transcriptionally arrested osteoblasts. This destabilization of osteonectin mRNA may be one means by which bFGF regulates extracellular matrix remodeling.

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