Temporomandibular joint degeneration arises spontaneously in STR/ort mice and is prevented by targeted aggrecanase inhibition

Kazuhiro Ooi , Kazuhiro Yamamoto , Yutaka Kobayashi , Behzad Javaheri , Anders Jensen , Ioannis Kanakis , Takao Sakai , Fadi Jarad , Hiroyuki Nakamura , Andrew A. Pitsillides , Shuichi Kawashiri , George Bou-Gharios
{"title":"Temporomandibular joint degeneration arises spontaneously in STR/ort mice and is prevented by targeted aggrecanase inhibition","authors":"Kazuhiro Ooi ,&nbsp;Kazuhiro Yamamoto ,&nbsp;Yutaka Kobayashi ,&nbsp;Behzad Javaheri ,&nbsp;Anders Jensen ,&nbsp;Ioannis Kanakis ,&nbsp;Takao Sakai ,&nbsp;Fadi Jarad ,&nbsp;Hiroyuki Nakamura ,&nbsp;Andrew A. Pitsillides ,&nbsp;Shuichi Kawashiri ,&nbsp;George Bou-Gharios","doi":"10.1016/j.ocarto.2025.100599","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Temporomandibular joint osteoarthritis (TMJ-OA) is painful and causes masticatory dysfunction, but current treatment is limited to symptom relief due to an incomplete appreciation of aetiology. Herein, we develop morphological and histological methods for quantitative evaluation of TMJ-OA severity and examine whether STR/Ort mice, which are genetically predisposed to spontaneous knee OA, exhibit protection against TMJ-OA upon genetic gain-of-function modification of an aggrecanase-selective mutant of tissue inhibitor of metalloproteinase (TIMP)-3.</div></div><div><h3>Design</h3><div>We established morphological changes in mandibular condylar head adapted from human TMJ-OA criteria, and developed and verified the utility of TMJ-OA histological damage scoring adapted from the OARSI system. Mutant TIMP3 containing an extra alanine at the N-Terminus ([-1A] TIMP-3 was overexpressed in STR/Ort and CBA mice. Morphological changes in mandibular condyle and TMJ cartilage degradation were evaluated and quantified using micro-CT and histology in mice aged 10, 20 and 40 weeks.</div></div><div><h3>Results</h3><div>Whilst no evidence of TMJ-OA was observed in STR/Ort mice aged 10 weeks, bone erosion and osteophyte formation appeared in the mandibular condyle by 20 weeks, with remarkable deformity and bone resorption at 40 weeks in STR/Ort, but not the parental CBA strain. TMJ-OA was less severe in 40 week-old [-1A]TIMP-3 overexpressing STR/Ort and CBA compared to wild-type mice.</div></div><div><h3>Conclusions</h3><div>Using our new mouse TMJ-OA scoring system we have found that OA affects joints other than the knee in the STR/Ort strain. Genetic gain-of-function modification of STR/Ort mice with an aggrecanase-selective mutant of tissue inhibitor of metalloproteinase (TIMP)-3 also affords in vivo chondroprotection against this TMJ-OA.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 2","pages":"Article 100599"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Osteoarthritis and cartilage open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2665913125000354","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

Temporomandibular joint osteoarthritis (TMJ-OA) is painful and causes masticatory dysfunction, but current treatment is limited to symptom relief due to an incomplete appreciation of aetiology. Herein, we develop morphological and histological methods for quantitative evaluation of TMJ-OA severity and examine whether STR/Ort mice, which are genetically predisposed to spontaneous knee OA, exhibit protection against TMJ-OA upon genetic gain-of-function modification of an aggrecanase-selective mutant of tissue inhibitor of metalloproteinase (TIMP)-3.

Design

We established morphological changes in mandibular condylar head adapted from human TMJ-OA criteria, and developed and verified the utility of TMJ-OA histological damage scoring adapted from the OARSI system. Mutant TIMP3 containing an extra alanine at the N-Terminus ([-1A] TIMP-3 was overexpressed in STR/Ort and CBA mice. Morphological changes in mandibular condyle and TMJ cartilage degradation were evaluated and quantified using micro-CT and histology in mice aged 10, 20 and 40 weeks.

Results

Whilst no evidence of TMJ-OA was observed in STR/Ort mice aged 10 weeks, bone erosion and osteophyte formation appeared in the mandibular condyle by 20 weeks, with remarkable deformity and bone resorption at 40 weeks in STR/Ort, but not the parental CBA strain. TMJ-OA was less severe in 40 week-old [-1A]TIMP-3 overexpressing STR/Ort and CBA compared to wild-type mice.

Conclusions

Using our new mouse TMJ-OA scoring system we have found that OA affects joints other than the knee in the STR/Ort strain. Genetic gain-of-function modification of STR/Ort mice with an aggrecanase-selective mutant of tissue inhibitor of metalloproteinase (TIMP)-3 also affords in vivo chondroprotection against this TMJ-OA.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Osteoarthritis and cartilage open
Osteoarthritis and cartilage open Orthopedics, Sports Medicine and Rehabilitation
CiteScore
3.30
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信