Age-related expression of molecular regulators of hypertrophy and maturation in articular cartilage.
Abstract: The purpose of this study was to determine changes in the expression of regulatory molecules in normal equine articular cartilage throughout development up to 18 months of age. The hypothesis was that expression of these regulatory molecules would decrease from birth to postpubescence. Cartilage was harvested from normal femoropatellar or scapulohumeral joints from 34 fresh horse cadavers. Horses were placed in four age groups [prenatal (n = 5); prepubertal, 0-6 months (n = 11); pubertal, 7-14 months (n = 13); and postpubertal, 15-18 months (n = 5)]. Indian hedgehog (Ihh), Gli1, Gli3, Patched1 (Ptc1), Smoothened (Smo), Noggin, bone morphogenetic protein-6 (BMP-6), BMP-2, parathyroid hormone-related peptide (PTHrP), and PTH/PTHrP receptor mRNA expression levels were evaluated by real-time quantitative PCR. Spatial tissue mRNA and protein expression was determined by in situ hybridization and immunohistochemistry. The expression of PTHrP decreased (p = 0.002) in the pubertal group, while PTH/PTHrP receptor expression significantly increased (p = 0.001). No significant difference was found between groups for Ihh (p = 0.6) or Smo (p = 0.3) expression. In contrast, there was significantly increased expression of Ptc1 (p = 0.006), Gli1 (p = 0.04), and Gli3 (p = 0.007) in the pubertal group, and Gli3 (p = 0.007) remained elevated in the postpubertal group. The expression of BMP-6 significantly increased from prenatal to postnatal groups (p = 0.03) while BMP-2 expression increased during puberty and postpuberty (p = 0.03). The changes in expression of hedgehog and BMP signaling molecules in articular cartilage during postnatal development have not been shown previously. The increased expression of hedgehog receptor and transcription factors during puberty may indicate maturation of the deep articular layer during this time period.
Publication Date: 2006-06-22 PubMed ID: 16788989DOI: 10.1002/jor.20227Google Scholar: Lookup
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- Journal Article
- Age Factors
- Anatomy
- Articular Cartilage
- Bones
- Cadaver
- Cartilage
- Cells
- Clinical Study
- Developmental Biology
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Genes
- Genetics
- Horses
- Immunohistochemistry
- In Situ Hybridization
- In Vivo
- Molecular biology
- Physiology
- Real-Time PCR
- Tissue
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research examines how the expression of certain regulatory molecules in horse articular cartilage changes from birth up till 18 months to provide insights into cartilage growth and maturation. The study particularly focuses on major molecules involved in cartilage development and hypothesizes a decrease in their expressions with growth.
Methodology
- The study is conducted on cartilage samples acquired from femoropatellar or scapulohumeral joints of horse cadavers. The number of cadavers sampled is 34.
- The horses are categorized into four age groups: prenatal, prepubertal (0-6 months), pubertal (7-14 months), and postpubertal (15-18 months).
- Molecular regulators under observation include the Indian hedgehog (Ihh), Gli1, Gli3, Patched1 (Ptc1), Smoothened (Smo), Noggin, bone morphogenetic proteins (BMP-6 and BMP-2), parathyroid hormone-related peptide (PTHrP), and PTH/PTHrP receptor.
- The expression levels of these molecules are evaluated using real-time quantitative PCR while their spatial tissue mRNA and protein expression are determined using in situ hybridization and immunohistochemistry.
Results
- In accordance with the study’s initial hypothesis, the expression of PTHrP decreased in the cartilage of the pubertal group. At the same time, PTH/PTHrP receptor expression was seen to increase significantly.
- No change was found in the expression of Ihh or Smo between groups.
- A significant increase in the expression of Ptc1, Gli1, and Gli3 was observed during puberty, with Gli3 remaining elevated even in the postpubertal group.
- Expressions of BMP-6 increased from the prenatal to the postnatal groups and BMP-2 expression increased during puberty and postpuberty.
Conclusions
- These findings mark the first account of changes in hedgehog and BMP signaling molecules in articular cartilage following birth. This provides valuable understanding into the mechanisms governing postnatal cartilage development in mammals.
- The increase in hedgehog receptor and transcription factors during puberty suggests maturation of the deep articular layer during this growth phase.
Cite This Article
APA
Semevolos SA, Nixon AJ, Fortier LA, Strassheim ML, Haupt J.
(2006).
Age-related expression of molecular regulators of hypertrophy and maturation in articular cartilage.
J Orthop Res, 24(8), 1773-1781.
https://doi.org/10.1002/jor.20227 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA. stacy.semevolos@oregonstate.edu
MeSH Terms
- Aging / physiology
- Animals
- Bone Morphogenetic Protein 2
- Bone Morphogenetic Protein 6
- Bone Morphogenetic Proteins / genetics
- Carrier Proteins / genetics
- Cartilage, Articular / cytology
- Cartilage, Articular / growth & development
- Cartilage, Articular / physiology
- Cell Differentiation / physiology
- Gene Expression Regulation, Developmental / physiology
- Hedgehog Proteins
- Horses
- Hypertrophy
- Kruppel-Like Transcription Factors / genetics
- Oncogene Proteins / genetics
- Parathyroid Hormone-Related Protein / genetics
- Patched Receptors
- RNA, Messenger / metabolism
- Receptor, Parathyroid Hormone, Type 1 / genetics
- Receptors, Cell Surface / genetics
- Receptors, G-Protein-Coupled / genetics
- Signal Transduction / physiology
- Trans-Activators / genetics
- Transforming Growth Factor beta / genetics
- Zinc Finger Protein GLI1
Citations
This article has been cited 5 times.- Bach FC, de Rooij KM, Riemers FM, Snuggs JW, de Jong WAM, Zhang Y, Creemers LB, Chan D, Le Maitre C, Tryfonidou MA. Hedgehog proteins and parathyroid hormone-related protein are involved in intervertebral disc maturation, degeneration, and calcification.. JOR Spine 2019 Dec;2(4):e1071.
- Fan Y, Jianying F, Chenyan L, Pan W, Zhe S, Changjing S. [Influence on Indian hedgehog-parathyroid hormone-like related protein pathway induced by altered masticatory loading in the condylar cartilage of growing rabbits].. Hua Xi Kou Qiang Yi Xue Za Zhi 2017 Apr 1;35(2):127-132.
- Lee JK, Gegg CA, Hu JC, Reddi AH, Athanasiou KA. Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage.. Arthritis Res Ther 2015 Feb 11;17(1):28.
- Chen X, Macica CM, Nasiri A, Broadus AE. Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone-related protein in mice.. Arthritis Rheum 2008 Dec;58(12):3788-97.
- Cheng C, Conte E, Pleshko-Camacho N, Hidaka C. Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein.. Matrix Biol 2007 Sep;26(7):541-53.
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