OBJECTIVE: To summarize the regulatory effect of non-coding RNA (ncRNA) on type H vessels angiogenesis of bone. METHODS: Recent domestic and foreign related literature about the regulation of ncRNA in type H vessels angiogenesis was widely reviewed and summarized. RESULTS: Type H vessels is a special subtype of bone vessels with the ability to couple bone formation. At present, the research on ncRNA regulating type H vessels angiogenesis in bone diseases mainly focuses on microRNA, long ncRNA, and small interfering RNA, which can affect the expressions of hypoxia inducible factor 1α, platelet derived growth factor BB, slit guidance ligand 3, and other factors through their own unique ways of action, thus regulating type H vessels angiogenesis and participating in the occurrence and development of bone diseases. CONCLUSION At present, the mechanism of ncRNA regulating bone type H vessels angiogenesis has been preliminarily explored. With the deepening of research, ncRNA is expected to be a new target for the diagnosis and treatment of vascular related bone diseases.
Humans ; RNA, Untranslated/genetics* ; RNA, Long Noncoding ; Bone Diseases/genetics* ; MicroRNAs/genetics* ; RNA, Small Interfering

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

BACKGROUND: Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear. METHODS: A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis. RESULTS: A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17 , DCLK1 , PCDH7 , TSPAN5 , NHSL2 , and CPT1B . Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group. CONCLUSION Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
Humans ; Adolescent ; Scoliosis/genetics* ; Cell Differentiation/physiology* ; Osteogenesis/genetics* ; Bone Diseases, Metabolic/genetics* ; Kyphosis ; Autophagy/genetics* ; Bone Marrow Cells ; Cells, Cultured ; Doublecortin-Like Kinases

Notch signaling is highly conserved in evolution and regarded as a key factor in cell fate determination. It mediates cell-to-cell interactions that are critical for embryonic development and tissue renewal, and is involved in the occurrence and metastasis of neoplasm. Recent researches have found that such signaling plays an important role in modulating the differentiation of chondrocytes, osteoblasts and osteoclasts. Dysfunction of Notch signaling can result in many skeletal diseases such as bone tumor, disorders of bone development or bone metabolism.
Animals ; Bone Development ; Bone Diseases ; genetics ; metabolism ; Bone and Bones ; metabolism ; Humans ; Osteoblasts ; cytology ; metabolism ; Osteogenesis ; Receptors, Notch ; genetics ; metabolism ; Signal Transduction

The TET gene family has been found a few years ago. Recent studies indicated that TET2 (TET gene family 2) plays an important role in DNA demethylation, the epigenetic regulation and normal hematopoiesis. TET2 mutation has been discovered in a spectrum of myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and leukemia, which suggest the role of TET2 as a tumor suppressor. In this review the recent results implicating TET2 in hematological malignancies are summarized, including regulatory functions of TET gene epigenetics, TET2 gene and hematopoietic regulation in bone marrow, TET2 gene and hematological disease(MPN, MDS, AML, CMML, lymphoma) and so on.
Bone Marrow ; metabolism ; DNA-Binding Proteins ; genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Hematologic Diseases ; genetics ; Humans ; Proto-Oncogene Proteins ; genetics

Vitamin K is the cofactor for the hepatic carboxylation of glutamic acid residues in a number of proteins including the procoagulants factors ll, Vll, lX, and X. The role of vitamin K in normal bone function is not fully understood. Inherited deficiency of vitamin K dependent coagulation factors is a rare bleeding disorder reported only in a few patients. Here we present an 18-month old child who presented with osteopeni due to inherited vitamin K deficiency. While the patient had high bone specific alkaline phosphatase and parathyroid hormone levels and low osteocalcin and bone mineral density values, with the regular supplementation of vitamin K all the mentioned parameters returned to normal values.
Bone Density ; Bone Diseases, Metabolic/etiology ; Human ; Infant ; Male ; Osteocalcin/blood ; Prothrombin Time ; Vitamin K Deficiency/blood/complications/*genetics

OBJECTIVE: To explore the clinical and genetic characteristics of three children with KBG syndrome. METHODS: Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. RESULTS: All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype. CONCLUSION The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.
Female ; Child ; Humans ; Abnormalities, Multiple/genetics* ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/genetics* ; Tooth Abnormalities/genetics* ; Facies ; Repressor Proteins/genetics* ; Mothers ; Mutation

OBJECTIVETo study clinical features and gene mutations in Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disease, in children.

METHODClinical manifestations, laboratory examinations, image studies, and genetic testing of two cases with SDS were presented, analyzed, and discussed; 311 SDS cases from the related literature since 2004 were reviewed.

RESULT(1) The two cases both presented with characteristic exocrine pancreatic insufficiency evidenced by abnormal pancreas on imaging and growth retardation, persistent or intermittent neutropenia (<1500×10(6)/L) and/or anemia, and skeletal abnormalities. Analysis of the SBDS gene revealed the same compound heterozygous genotype (c.183_184TA > CT, c.258+2T > C) for both subjects. This genotype is the result of the inheritance of abnormal alleles from both healthy parents. (2) Among 311 cases, 75 cases having complete clinical data were characterized by exocrine pancreatic dysfunction (61/75; 81.3%), hematologic abnormalities with single- or multi-lineage cytopenia (64/75; 85.3%), and bone abnormalities (47/75; 62.7%). c.183_184TA > CT, c.258+2T > C, and c. [ 183_184TA > CT; 258+2T > C] are the major types of SBDS gene mutation(85/138;61.6%).

CONCLUSIONSDS is characterized by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multi-lineage cytopenia, and bone abnormalities. The diagnosis of SDS relies on a combination of clinical features and gene-based tests. The SDS patients need long term follow-up and management.

Bone Marrow Diseases ; diagnosis ; genetics ; Child ; DNA Mutational Analysis ; Exocrine Pancreatic Insufficiency ; diagnosis ; genetics ; Exons ; Genes, Recessive ; Heterozygote ; Humans ; Infant ; Lipomatosis ; diagnosis ; genetics ; Male ; Mutation ; Neutropenia ; Proteins ; genetics

OBJECTIVEPolyethylene glycol/bone morphogenetic protein-2 (PEG/BMP-2) nanoparticles were transfected into Rabbit bone mesenchymal stem cells (rBMSCs) and the expression of BMP-2 was detected.

METHODSDissociated rBMSCs were primarily cultured in vitro and BMP-2 gene was transfected into rBMSCs by PEG/BMP-2 nanoparticals and lipofectamine, respectively. The efficiency of transfection was detected by flow cytometry and the expression of BMP-2 was detected by Western Blot and real time RT-PCR.

RESULTSPEG/BMP-2 nanoparticals were successfully synthesized and transfected into rBMSCs. Compared with the lipofectamine transfection group, PEG/BMP-2 transfection group had higher efficiency and higher BMP-2 expression.

CONCLUSIONPEG/BMP-2 nanoparticals transfected rBMSCs highly expressed BMP-2,which provided novel strategies for the treatment of bone defect.

Animals ; Bone Diseases ; genetics ; therapy ; Bone Morphogenetic Protein 2 ; chemistry ; genetics ; metabolism ; Bone and Bones ; cytology ; Gene Expression Regulation ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Nanoparticles ; chemistry ; Polyethylene Glycols ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Rabbits ; Transfection ; methods

Bone Marrow Diseases ; diagnosis ; genetics ; therapy ; Child, Preschool ; Exocrine Pancreatic Insufficiency ; diagnosis ; genetics ; therapy ; Female ; Humans ; Infant ; Lipomatosis ; diagnosis ; genetics ; therapy ; Male ; Mutation