TY - JOUR
T1 - Impairment of Cyclo-oxygenase-2 Function Results in Abnormal Growth Plate Development and Bone Microarchitecture but Does Not Affect Longitudinal Growth of the Long Bones in Skeletally Immature Mice
AU - Caron, Marjolein M J
AU - Castermans, Tessy M R
AU - van Rietbergen, Bert
AU - Haartmans, Mirella J J
AU - van Rhijn, Lodewijk W
AU - Witlox, Adhiambo M A
AU - Welting, Tim J M
N1 - Funding Information:
The authors would like to thank the employees of the animal facility of the Maastricht University Medical Center (MUMC) for their assistance during this study and Dr. M. Poeze (Department of General Surgery, MUMC, the Netherlands) for providing the mice. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The authors thank the Dutch Arthritis Association (Grant LLP14), the Dutch Stichting Annafonds | NOREF (Grant O2012/66) for their financial support.
Publisher Copyright:
© The Author(s) 2019.
PY - 2021/7
Y1 - 2021/7
N2 - OBJECTIVE: Despite the general awareness that cyclo-oxygenase-2 (COX-2) is crucial for endochondral ossification, the role of COX-2 in skeletal development is largely unknown. We hypothesized that inhibition or genetic loss of COX-2 leads to impaired growth plate development and consequently impaired postnatal development of the long bones.DESIGN: Skeletally immature (5 weeks old) B6;129S-Ptgs2tm1Jed/J wildtype mice were treated for 10 weeks with celecoxib (daily oral administration 10 mg/kg) or placebo and compared with B6;129S-Ptgs2tm1Jed/J homozygous knockout mice (n = 12 per group).RESULTS: Fifteen weeks postnatally, no significant difference in growth plate (zone) thickness was found between groups. However, significantly higher proteoglycan content and lower expression levels of collagen type II and X staining in the growth plates of celecoxib-treated mice, and to a lesser extent in COX-2 knockout mice. In addition, a significantly decreased cell number and cell size were observed in the hypertrophic zone of the growth plates of both experimental groups. Micro-computed tomography analysis of the subchondral bone region directly beneath the growth plate showed significantly higher bone density and trabecular thickness, following celecoxib treatment. Despite the detected differences in growth plate extracellular matrix composition and subchondral bone morphology, no difference was found in the length of the tibia in celecoxib-treated mice or COX-2 knockout mice.CONCLUSIONS: Genetic loss of COX-2 or treatment with celecoxib did not result in detectable differences in gross murine formation of the tibia or femur. However, there were notable phenotypic features detected in the maturation of the growth plate (hypertrophic zone and subchondral bone) as a result of the celecoxib treatment.
AB - OBJECTIVE: Despite the general awareness that cyclo-oxygenase-2 (COX-2) is crucial for endochondral ossification, the role of COX-2 in skeletal development is largely unknown. We hypothesized that inhibition or genetic loss of COX-2 leads to impaired growth plate development and consequently impaired postnatal development of the long bones.DESIGN: Skeletally immature (5 weeks old) B6;129S-Ptgs2tm1Jed/J wildtype mice were treated for 10 weeks with celecoxib (daily oral administration 10 mg/kg) or placebo and compared with B6;129S-Ptgs2tm1Jed/J homozygous knockout mice (n = 12 per group).RESULTS: Fifteen weeks postnatally, no significant difference in growth plate (zone) thickness was found between groups. However, significantly higher proteoglycan content and lower expression levels of collagen type II and X staining in the growth plates of celecoxib-treated mice, and to a lesser extent in COX-2 knockout mice. In addition, a significantly decreased cell number and cell size were observed in the hypertrophic zone of the growth plates of both experimental groups. Micro-computed tomography analysis of the subchondral bone region directly beneath the growth plate showed significantly higher bone density and trabecular thickness, following celecoxib treatment. Despite the detected differences in growth plate extracellular matrix composition and subchondral bone morphology, no difference was found in the length of the tibia in celecoxib-treated mice or COX-2 knockout mice.CONCLUSIONS: Genetic loss of COX-2 or treatment with celecoxib did not result in detectable differences in gross murine formation of the tibia or femur. However, there were notable phenotypic features detected in the maturation of the growth plate (hypertrophic zone and subchondral bone) as a result of the celecoxib treatment.
KW - Animals
KW - Bone and Bones
KW - Celecoxib/pharmacology
KW - Cyclooxygenase 2/genetics
KW - Growth Plate
KW - Mice
KW - X-Ray Microtomography
U2 - 10.1177/1947603519833149
DO - 10.1177/1947603519833149
M3 - Article
C2 - 30880429
SN - 1947-6035
VL - 12
SP - 387
EP - 398
JO - Cartilage
JF - Cartilage
IS - 3
ER -