2. Academic Validation
  3. Ano5 deficiency disturbed bone formation by inducing osteoclast apoptosis in Gnathodiaphyseal dysplasia

Ano5 deficiency disturbed bone formation by inducing osteoclast apoptosis in Gnathodiaphyseal dysplasia

  • Exp Cell Res. 2025 Apr 1;447(1):114493. doi: 10.1016/j.yexcr.2025.114493.
Xiu Liu 1,  Shengnan Wang 2,  Chao Liang 3,  Shuai Zhang 4,  Sirui Liu 5,  Ying Hu 6
Affiliations

Affiliations

  • 1 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: liuxiu1206@foxmail.com.
  • 2 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: wangsn1101@yeah.net.
  • 3 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100050, China. Electronic address: lcjims@163.com.
  • 4 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: zskqdoctor@126.com.
  • 5 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: 595232480@qq.com.
  • 6 Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: shuaiyu369@163.com.
PMID: 40049314 DOI: 10.1016/j.yexcr.2025.114493
Abstract

Gnathodiaphyseal dysplasia (GDD) is a rare genetic syndrome characterized by cemento-ossifying fibroma lesions in the mandible and sclerosis of tubular bones. Currently, the clinical treatment of GDD is limited to surgical resection; therefore, novel treatment strategies developed through exploration of the related mechanisms are needed. Mutations in the TMEM16E/ANO5 gene are considered the main pathogenic factor of GDD, and the Ano5 knockout mouse model (Ano5-/-) established previously, which presented GDD-like characteristics, exhibited decreased osteoclastogenesis. ANO5, a calcium-activated Chloride Channel (CaCC), plays an important role in the maintenance of intracellular calcium homeostasis, which is crucial for osteoclast differentiation. In this study, our data indicated that the intracellular calcium concentration ([CA2+]i) and calcium transients were significantly decreased in Ano5-/- osteoclasts accompanied by abnormally altered expression of calcium transporters, resulting in calcium dyshomeostasis. In addition, the endoplasmic reticulum stress (ERS) response was significantly enhanced in Ano5-/- osteoclasts, possibly because of calcium dyshomeostasis, which leading to the increased proportion of apoptotic osteoclasts via the activation of the C/EBP homologous protein (CHOP) signalling pathway, accompanied by abnormal changes in the expression of apoptosis-related factors. In summary, Ano5 deficiency impairs the function of osteoclasts by increasing osteoclast Apoptosis, which is induced by an overactivated ERS response via calcium dyshomeostasis.

Keywords

Ano5(−/−) osteoclasts; Calcium dyshomeostasis; Cell apoptosis; Endoplasmic reticulum stress; Gnathodiaphyseal dysplasia.

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