Impact of Mechanical Strain and Nicotinamide on RUNX2-Deficient Osteoblast Mimicking Cleidocranial Dysplasia

Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. N...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-12, Vol.24 (23), p.16581
Main Authors: Schröder, Agnes, Örs, Talia, Byeon, Ye-Oun, Cieplik, Fabian, Proff, Peter, Kirschneck, Christian, Paddenberg, Eva
Format: Article
Language:English
Subjects:
bone remodeling
cleidocranial dysplasia (CCD)
Cytokines
Cytotoxicity
Dysplasia
Gene expression
Genes
Genetic aspects
Genetic transcription
Interleukins
Ligaments
Ligands
mechanical strain
Medical research
Medicine, Experimental
Niacinamide
orthodontic tooth movement
Orthodontics
Physiological aspects
Protein expression
Proteins
Transcription factors
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Summary:Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. Nicotinamide (NAM) affects bone remodelling processes. As these are crucial for orthodontic therapy, NAM could improve orthodontic treatment in CCD patients. This study investigates the effect of NAM in control and RUNX2-deficient osteoblasts under mechanical strain mimicking orthodontic treatment. First, the optimal NAM concentration and the differences in the expression profile of control and RUNX2-deficient osteoblasts were determined. Subsequently, osteoblasts were exposed to tensile and compressive strain with and without NAM, and the expression of genes critically involved in bone remodelling was investigated. NAM increased the expression of bone remodelling genes. RUNX2-deficient osteoblasts expressed more receptor activator of NFkB ligand (RANKL) and interleukin-6 (IL6), but less colony-stimulating factor-1 (CSF1). Most of the positive effects of NAM on bone remodelling genes were impaired by mechanical loading. In conclusion, NAM stimulated osteoblast differentiation by increasing the expression of RUNX2 and regulated the expression of osteoclastogenic factors. However, the positive effects of NAM on bone metabolism were impaired by mechanical loading and RUNX2 deficiency.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242316581