Abstract
Objective
To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification.Design
Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n = 7) or 7 (n = 5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFβ1 and Indian hedgehog was performed.Results
By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63 μm (95% CI -103, -22) and -19 μm (95% CI -33, -5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311 μm (95% CI -542, -82) in all ischemic samples. TGFβ1 expression was increased in the hypertrophic zone at 7 days post-ischemia.Conclusions
Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD.References
Articles referenced by this article (35)
Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.
PLoS Genet, (10):e1006352 2016
MED: 27741240
Premature femoral neck physeal closure in Perthes' disease.
Clin Orthop Relat Res, (171):24-29 1982
MED: 7140075
Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes.
Microsc Res Tech, (6):505-519 1994
MED: 7949396
Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calve-Perthes disease.
Osteoarthritis Cartilage, (9):1244-1253 2022
MED: 35644462
Epiphysial infarction in a growing long bone. An experimental study in the rabbit.
J Bone Joint Surg Br, (4):826-840 1966
MED: 5953817
Quantitative histomorphometric analysis of the human growth plate from birth to adolescence.
Bone, (4):495-501 2000
MED: 11033444
Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg-calve-perthes disease.
J Magn Reson Imaging, (1):106-113 2018
MED: 30556613
TGFbeta and PTHrP control chondrocyte proliferation by activating cyclin D1 expression.
Mol Biol Cell, (12):3852-3863 2001
MED: 11739785
Show 10 more references (10 of 35)
Citations & impact
Impact metrics
Alternative metrics
Discover the attention surrounding your research
https://www.altmetric.com/details/142098651
Article citations
Detection of early metaphyseal changes in a piglet model of Legg-Calvé-Perthes disease using quantitative mapping of MRI relaxation times.
J Orthop Res, 42(10):2277-2286, 26 May 2024
Cited by: 0 articles | PMID: 38796746 | PMCID: PMC11486590
Similar Articles
To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease.
Osteoarthritis Cartilage, 30(9):1244-1253, 26 May 2022
Cited by: 2 articles | PMID: 35644462 | PMCID: PMC9378508
Detection of early metaphyseal changes in a piglet model of Legg-Calvé-Perthes disease using quantitative mapping of MRI relaxation times.
J Orthop Res, 42(10):2277-2286, 26 May 2024
Cited by: 0 articles | PMID: 38796746 | PMCID: PMC11486590
Increased VEGF expression in the epiphyseal cartilage after ischemic necrosis of the capital femoral epiphysis.
J Bone Miner Res, 19(12):2041-2048, 20 Sep 2004
Cited by: 34 articles | PMID: 15537448
Legg-Calvé-Perthes disease overview.
Orphanet J Rare Dis, 17(1):125, 15 Mar 2022
Cited by: 14 articles | PMID: 35292045 | PMCID: PMC8922924
Review Free full text in Europe PMC
Funding
Funders who supported this work.
NCATS NIH HHS (1)
Grant ID: UL1 TR002494
NIAMS NIH HHS (3)
Grant ID: K01 AR070894
Grant ID: T32 AR050938
Grant ID: R56 AR078315
NIH HHS (2)
Grant ID: K01 OD021293
Grant ID: T32 OD010993
National Center for Advancing Translational Sciences (1)
Grant ID: UL1TR002494
National Institute of Arthritis and Musculoskeletal and Skin Diseases (3)
Grant ID: T32AR050938
Grant ID: R56AR078315
Grant ID: K01AR070894
National Institutes of Health (2)
Grant ID: K01OD021293
Grant ID: T32OD010993