A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis
Autosomal dominant osteopetrosis type II (ADO II), characterized by increased bone mass and density, is caused by mutations in the chloride channel 7 (CLCN7) gene. In this study, a novel missense variant in CLCN7 (c.1678A > G; p.Met560Val) was identified in three symptomatic subjects and one...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-11-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.599826/full |
| _version_ | 1828852384258850816 |
|---|---|
| author | Hui Peng Hong-Bo He Ting Wen |
| author_facet | Hui Peng Hong-Bo He Ting Wen |
| author_sort | Hui Peng |
| collection | DOAJ |
| description | Autosomal dominant osteopetrosis type II (ADO II), characterized by increased bone mass and density, is caused by mutations in the chloride channel 7 (CLCN7) gene. In this study, a novel missense variant in CLCN7 (c.1678A > G; p.Met560Val) was identified in three symptomatic subjects and one carrier of a Chinese family with ADO II. Notably, bone formation markers, including osteocalcin and total procollagen type N-terminal propeptide, have increased or presented at the upper limit of the normal range in the three patients. Serum factors secreted by osteoclast lineage cells and affecting the CD31hiEMCNhi vessel formation, such as tartrate-resistant acid phosphatase 5b, platelet-derived growth factor-BB, vascular endothelial growth factor, and SLIT3, had a higher expression in three ADO II subjects than in 15 healthy age-matched and sex-matched controls. Moreover, the conditioned medium was obtained from preosteoclast induced from the ADO II patients’ peripheral blood mononuclear cells. It was found to promote the CD31hiEMCNhi vessel formation of human microvascular endothelial cells and osteogenic differentiation of bone marrow-derived stem cells. Taken together, our finding revealed a novel CLCN7 variant associated with ADO II and suggested that the sclerotic bone was potentially associated with the increase of the CD31hiEMCNhi vessel formation and bone formation. |
| first_indexed | 2024-12-12T23:52:02Z |
| format | Article |
| id | doaj.art-f9a7137837924028884d611b6f98acd4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T23:52:02Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f9a7137837924028884d611b6f98acd42022-12-22T00:06:40ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.599826599826A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and OsteogenesisHui Peng0Hong-Bo He1Ting Wen2Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Orthopedic, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Orthopedic, Xiangya Hospital of Central South University, Changsha, ChinaAutosomal dominant osteopetrosis type II (ADO II), characterized by increased bone mass and density, is caused by mutations in the chloride channel 7 (CLCN7) gene. In this study, a novel missense variant in CLCN7 (c.1678A > G; p.Met560Val) was identified in three symptomatic subjects and one carrier of a Chinese family with ADO II. Notably, bone formation markers, including osteocalcin and total procollagen type N-terminal propeptide, have increased or presented at the upper limit of the normal range in the three patients. Serum factors secreted by osteoclast lineage cells and affecting the CD31hiEMCNhi vessel formation, such as tartrate-resistant acid phosphatase 5b, platelet-derived growth factor-BB, vascular endothelial growth factor, and SLIT3, had a higher expression in three ADO II subjects than in 15 healthy age-matched and sex-matched controls. Moreover, the conditioned medium was obtained from preosteoclast induced from the ADO II patients’ peripheral blood mononuclear cells. It was found to promote the CD31hiEMCNhi vessel formation of human microvascular endothelial cells and osteogenic differentiation of bone marrow-derived stem cells. Taken together, our finding revealed a novel CLCN7 variant associated with ADO II and suggested that the sclerotic bone was potentially associated with the increase of the CD31hiEMCNhi vessel formation and bone formation.https://www.frontiersin.org/articles/10.3389/fcell.2020.599826/fullautosomal dominant osteopetrosis type IICLCN7variantCD31hiEmcnhi vessel formationbone formation |
| spellingShingle | Hui Peng Hong-Bo He Ting Wen A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis Frontiers in Cell and Developmental Biology autosomal dominant osteopetrosis type II CLCN7 variant CD31hiEmcnhi vessel formation bone formation |
| title | A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis |
| title_full | A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis |
| title_fullStr | A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis |
| title_full_unstemmed | A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis |
| title_short | A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis |
| title_sort | novel variant in clcn7 regulates the coupling of angiogenesis and osteogenesis |
| topic | autosomal dominant osteopetrosis type II CLCN7 variant CD31hiEmcnhi vessel formation bone formation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.599826/full |
| work_keys_str_mv | AT huipeng anovelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis AT hongbohe anovelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis AT tingwen anovelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis AT huipeng novelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis AT hongbohe novelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis AT tingwen novelvariantinclcn7regulatesthecouplingofangiogenesisandosteogenesis |