Kindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis.
Identifying patient mutations driving skeletal development disorders has driven our understanding of bone development. Integrin adhesion deficiency disease is caused by a Kindlin-3 (fermitin family member 3) mutation, and its inactivation results in bleeding disorders and osteopenia. In this study, we uncover a role for Kindlin-3 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) down the chondrogenic lineage. Kindlin-3 expression increased with chondrogenic differentiation, similar to RUNX2. BMSCs isolated from a Kindlin-3 deficient patient expressed chondrocyte markers, including SOX9, under basal conditions, which were further enhanced with chondrogenic differentiation. Rescue of integrin activation by a constitutively activated β3 integrin construct increased adhesion to multiple extracellular matrices and reduced SOX9 expression to basal levels. Growth plates from mice expressing a mutated Kindlin-3 with the integrin binding site ablated demonstrated alterations in chondrocyte maturation similar to that seen with the human Kindlin-3 deficient BMSCs. These findings suggest that Kindlin-3 expression mirrors RUNX2 during chondrogenesis.
Pubmed ID: 33417921 RIS Download
Research resources used in this publication
- GraphPad Prism (RRID:SCR_002798) (software resource)
- BIOQUANT Life Science (RRID:SCR_016423) (software resource)
- SoftMax Pro Data Acquisition and Analysis Software (RRID:SCR_014240) (software resource)
- ImageJ (RRID:SCR_003070) (software resource)
- Leica TCS SPE (RRID:SCR_002140) (instrument resource)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Rabbit Anti-Collagen X Polyclonal Antibody, Unconjugated (RRID:AB_879742)
- CD11b Monoclonal Antibody (ICRF44), PE, eBioscience (RRID:AB_2043799)
- Mouse Anti-Human CD73 Monoclonal Antibody, PE Conjugated, Clone AD2 (RRID:AB_2033967)
- Rabbit Anti-Collagen II Polyclonal Antibody, Unconjugated (RRID:AB_731688)
- Anti-SOX9 antibody (RRID:AB_2728660)
- FITC anti-human CD34 (RRID:AB_1731852)
- PE/Cyanine7 anti-human CD117 (c-kit) (RRID:AB_893228)
- FITC anti-human CD105 (RRID:AB_755956)
- PE anti-human CD29 (RRID:AB_314320)
- CD45 FITC 2D1 CE (RRID:AB_2732010)
- Human Alkaline Phosphatase/ALPL APC-conjugated Antibody (RRID:AB_357039)
- IRDye 800CW Donkey anti-Rabbit IgG (RRID:AB_621848)
- VECTASHIELD Mounting Medium with DAPI (RRID:AB_2336790)
- Goat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_143165)
Associated grants
- Agency: NHLBI NIH HHS, United States
Id: R01 HL071625 - Agency: NCI NIH HHS, United States
Id: K99 CA175291 - Agency: NHLBI NIH HHS, United States
Id: P01 HL073311 - Agency: NCI NIH HHS, United States
Id: F32 CA142133 - Agency: NHLBI NIH HHS, United States
Id: R01 HL142772
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This is a list of tools and resources that we have found mentioned in this publication.
Rabbit Anti-Collagen X Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_879742
This polyclonal targets Collagen X
View all literature mentionsCD11b Monoclonal Antibody (ICRF44), PE, eBioscience (antibody)
RRID:AB_2043799
This monoclonal targets CD11b
View all literature mentionsMouse Anti-Human CD73 Monoclonal Antibody, PE Conjugated, Clone AD2 (antibody)
RRID:AB_2033967
This monoclonal targets Human CD73
View all literature mentionsRabbit Anti-Collagen II Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_731688
This polyclonal targets Collagen II
View all literature mentionsAnti-SOX9 antibody (antibody)
RRID:AB_2728660
This monoclonal targets SOX9
View all literature mentionsFITC anti-human CD34 (antibody)
RRID:AB_1731852
This monoclonal targets CD34
View all literature mentionsPE/Cyanine7 anti-human CD117 (c-kit) (antibody)
RRID:AB_893228
This monoclonal targets CD117
View all literature mentionsFITC anti-human CD105 (antibody)
RRID:AB_755956
This monoclonal targets CD105
View all literature mentionsPE anti-human CD29 (antibody)
RRID:AB_314320
This monoclonal targets CD29
View all literature mentionsCD45 FITC 2D1 CE (antibody)
RRID:AB_2732010
This monoclonal targets CD45
View all literature mentionsHuman Alkaline Phosphatase/ALPL APC-conjugated Antibody (antibody)
RRID:AB_357039
This monoclonal targets Alkaline Phosphatase
View all literature mentionsIRDye 800CW Donkey anti-Rabbit IgG (antibody)
RRID:AB_621848
This unknown targets IgG
View all literature mentionsVECTASHIELD Mounting Medium with DAPI (antibody)
RRID:AB_2336790
This unknown targets
View all literature mentionsGoat Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_143165
This polyclonal targets IgG (H+L)
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsBIOQUANT Life Science (software resource)
RRID:SCR_016423
Software tool to collect and analyse data on images of tissue slides or welled plates.Supports high-throughput immunofluorescence and immunohistochemistry, stereology, densitometry, and 3D modeling. Used in bioscience research in animal models and human biopsy, developmental neuroscience, traumatic brain/spinal cord injury, glaucoma, eye-movement disorders, cardiovascular disease and muscle disorders.
View all literature mentionsSoftMax Pro Data Acquisition and Analysis Software (software resource)
RRID:SCR_014240
A software package for microplate reader control and microplate data analysis. It includes analysis templates for a variety of assays run on Molecular Devices microplate readers.
View all literature mentionsImageJ (software resource)
RRID:SCR_003070
Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsLeica TCS SPE (instrument resource)
RRID:SCR_002140
High resolution, compact and robust confocal that enables immunohistochemical colocalization analysis of florescent markers.
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