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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load
Journal of bone and mineral research, v 37(6), pp 1097-1116
13 Feb 2022
PMID: 35060644
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Articular cartilage (AC) is essential for body movement but is highly susceptible to degenerative diseases and has poor self-repair capacity. To improve current subpar regenerative treatments, developmental mechanisms of AC should be clarified and, specifically, how its postnatal multizone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis. Although their importance for chondrocyte function is appreciated, their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach (Ift88-flox) targeting joint-lineage progenitors (Gdf5Cre) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected. However, mature AC (aged 2 months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30%-50%. In addition, and unexpectedly, we discovered that tidemark patterning was severely disrupted, as was hedgehog signaling, and exhibited specificity based on regional load-bearing functions of AC. Interestingly, Prg4 expression was markedly increased in highly loaded sites in mutants. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis including tidemark topography, zonal matrix composition, and ambulation load responses. (c) 2022 American Society for Bone and Mineral Research (ASBMR).
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Details
- Title
- Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load
- Creators
- Danielle Rux - Children's Hospital of PhiladelphiaKimberly Helbig - Children's Hospital of PhiladelphiaBiao Han - Drexel UniversityCourtney Cortese - Children's Hospital of PhiladelphiaEiki Koyama - Children's Hospital of PhiladelphiaLin Han - Drexel UniversityMaurizio Pacifici - Children's Hospital of Philadelphia
- Publication Details
- Journal of bone and mineral research, v 37(6), pp 1097-1116
- Publisher
- Wiley
- Number of pages
- 20
- Grant note
- F32AR074227; R01AR062908; R01AR074490; P30AR069619 / NIH/NIAMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000757991300001
- Scopus ID
- 2-s2.0-85124536341
- Other Identifier
- 991019168746204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism