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. 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 24(2023), 23 vom: 21. Nov. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Schröder, Agnes [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Bone remodeling |
|---|
| Anmerkungen: |
Date Completed 12.01.2024 Date Revised 12.01.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms242316581 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365597171 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365597171 | ||
| 003 | DE-627 | ||
| 005 | 20240114234814.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms242316581 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1258.xml |
| 035 | |a (DE-627)NLM365597171 | ||
| 035 | |a (NLM)38068903 | ||
| 035 | |a (PII)16581 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Schröder, Agnes |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of Mechanical Strain and Nicotinamide on RUNX2-Deficient Osteoblast Mimicking Cleidocranial Dysplasia |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.01.2024 | ||
| 500 | |a Date Revised 12.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a bone remodeling | |
| 650 | 4 | |a cleidocranial dysplasia (CCD) | |
| 650 | 4 | |a mechanical strain | |
| 650 | 4 | |a orthodontic tooth movement | |
| 650 | 7 | |a Core Binding Factor Alpha 1 Subunit |2 NLM | |
| 650 | 7 | |a RUNX2 protein, human |2 NLM | |
| 700 | 1 | |a Örs, Talia |e verfasserin |4 aut | |
| 700 | 1 | |a Byeon, Ye-Oun |e verfasserin |4 aut | |
| 700 | 1 | |a Cieplik, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Proff, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Kirschneck, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Paddenberg, Eva |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 23 vom: 21. Nov. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:23 |g day:21 |g month:11 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms242316581 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 23 |b 21 |c 11 | ||