Targeted and sustained Sox9 expression in mouse hypertrophic chondrocytes causes severe and spontaneous osteoarthritis by perturbing cartilage homeostasis
AJTR Copyright © 2020..
Sox9 is the master transcription factor essential for cartilage development and homeostasis. To investigate the specific role of Sox9 during chondrocyte hypertrophy, we generated a novel Col10a1-Sox9 transgenic mouse model, in which Sox9 is specifically expressed in hypertrophic chondrocytes driven by a well-characterized 10-kb Col10a1 promoter. These mice were viable and fertile, and appeared normal at birth. However, they developed dwarfism by ten weeks of age. The histological analysis of the growth plates from these transgenic mice demonstrated an abnormal growth plate architecture and a significantly reduced amount of trabecular bone and mineral content in the primary spongiosa. Real-time qPCR analysis revealed the reduced expression of Col10a1, and increased expressions of adipogenic differentiation markers in primary hypertrophic chondrocytes isolated from transgenic mice. Concomitantly, the transgenic mouse chondrocyte cultures had increased lipid droplet accumulation. Unexpectedly, we also observed an increased incidence of spontaneous osteoarthritis (OA) development in the transgenic mice by X-ray analysis, micro-computed tomography scanning, and histological examination of knee joints. The manifestation of OA in Col10a1-Sox9 transgenic mice began by six-months of age, and worsened by eleven-months of age. In conclusion, we provide strong evidence that the proper spatiotemporal expression of Sox9 is necessary for normal adult hypertrophic cartilage homeostasis, and that the aberrant expression of Sox9 might lead to spontaneous OA development.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
American journal of translational research - 12(2020), 3 vom: 08., Seite 1056-1069 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liang, Bojian [VerfasserIn] |
|---|
| Themen: |
Adipogenesis |
|---|
| Anmerkungen: |
Date Revised 25.04.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM308549252 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM308549252 | ||
| 003 | DE-627 | ||
| 005 | 20240425232014.0 | ||
| 007 | tu | ||
| 008 | 231225s2020 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n1386.xml |
| 035 | |a (DE-627)NLM308549252 | ||
| 035 | |a (NLM)32269734 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liang, Bojian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Targeted and sustained Sox9 expression in mouse hypertrophic chondrocytes causes severe and spontaneous osteoarthritis by perturbing cartilage homeostasis |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a AJTR Copyright © 2020. | ||
| 520 | |a Sox9 is the master transcription factor essential for cartilage development and homeostasis. To investigate the specific role of Sox9 during chondrocyte hypertrophy, we generated a novel Col10a1-Sox9 transgenic mouse model, in which Sox9 is specifically expressed in hypertrophic chondrocytes driven by a well-characterized 10-kb Col10a1 promoter. These mice were viable and fertile, and appeared normal at birth. However, they developed dwarfism by ten weeks of age. The histological analysis of the growth plates from these transgenic mice demonstrated an abnormal growth plate architecture and a significantly reduced amount of trabecular bone and mineral content in the primary spongiosa. Real-time qPCR analysis revealed the reduced expression of Col10a1, and increased expressions of adipogenic differentiation markers in primary hypertrophic chondrocytes isolated from transgenic mice. Concomitantly, the transgenic mouse chondrocyte cultures had increased lipid droplet accumulation. Unexpectedly, we also observed an increased incidence of spontaneous osteoarthritis (OA) development in the transgenic mice by X-ray analysis, micro-computed tomography scanning, and histological examination of knee joints. The manifestation of OA in Col10a1-Sox9 transgenic mice began by six-months of age, and worsened by eleven-months of age. In conclusion, we provide strong evidence that the proper spatiotemporal expression of Sox9 is necessary for normal adult hypertrophic cartilage homeostasis, and that the aberrant expression of Sox9 might lead to spontaneous OA development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Col10a1 | |
| 650 | 4 | |a Hypertrophic chondrocytes | |
| 650 | 4 | |a Sox9 | |
| 650 | 4 | |a adipogenesis | |
| 650 | 4 | |a osteoarthritis | |
| 700 | 1 | |a Mamidi, Murali K |e verfasserin |4 aut | |
| 700 | 1 | |a Samsa, William E |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Brendan |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Qiping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Guang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of translational research |d 2009 |g 12(2020), 3 vom: 08., Seite 1056-1069 |w (DE-627)NLM193229463 |x 1943-8141 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2020 |g number:3 |g day:08 |g pages:1056-1069 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2020 |e 3 |b 08 |h 1056-1069 | ||