Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR.
J Bone Miner Res
; 34(4): 726-738, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30496623
ABSTRACT
Traumatic joint injuries produce osteoarthritic cartilage manifesting accelerated chondrocyte terminal differentiation and matrix degradation via unknown cellular and molecular mechanisms. Here we report the ability of biomechanical stress to increase expression of the calcium-sensing receptor (CaSR), a pivotal driver of chondrocyte terminal differentiation, in cultured chondrogenic cells subjected to fluid flow shear stress (FFSS) and in chondrocytes of rodent temporomandibular joint (TMJ) cartilage subjected to unilateral anterior cross-bite (UAC). In cultured ATDC5 cells or TMJ chondrocytes, FFSS induced Ca2+ loading and CaSR localization in endoplasmic reticulum (ER), casually accelerating cell differentiation that could be abrogated by emptying ER Ca2+ stores or CaSR knockdown. Likewise, acute chondrocyte-specific Casr knockout (KO) prevented the UAC-induced acceleration of chondrocyte terminal differentiation and matrix degradation in TMJ cartilage in mice. More importantly, local injections of CaSR antagonist, NPS2143, replicated the effects of Casr KO in preventing the development of osteoarthritic phenotypes in TMJ cartilage of the UAC-treated rats. Our study revealed a novel pathological action of CaSR in development of osteoarthritic cartilage due to aberrant mechanical stimuli and supports a therapeutic potential of calcilytics in preventing osteoarthritis in temporomandibular joints by targeting the CaSR. © 2018 American Society for Bone and Mineral Research.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Articulação Temporomandibular
/
Transtornos da Articulação Temporomandibular
/
Condrócitos
/
Receptores de Detecção de Cálcio
/
Naftalenos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Bone Miner Res
Assunto da revista:
METABOLISMO
/
ORTOPEDIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China