title: Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading.
abstract: Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 functions, by examining expression in cartilage during mouse and human osteoarthritis (OA) progression and in response to mechanical loading. Spared and diseased compartments in knees of OA patients and in mice with surgical destabilization of the medial meniscus were examined for changes in expression of Runx1 mRNA (Q-PCR) and protein (immunoblot, immunohistochemistry). Runx1 levels were quantified in response to static mechanical compression of bovine articular cartilage. Runx1 function was assessed by cell proliferation (Ki67, PCNA) and cell type phenotypic markers. Runx1 is enriched in superficial zone (SZ) chondrocytes of normal bovine, mouse, and human tissues. Increasing loading conditions in bovine cartilage revealed a positive correlation with a significant elevation of Runx1. Runx1 becomes highly expressed at the periphery of mouse OA lesions and in human OA chondrocyte 'clones' where Runx1 co-localizes with Vcam1, the mesenchymal stem cell (MSC) marker and lubricin (Prg4), a cartilage chondroprotective protein. These OA induced cells represent a proliferative cell population, Runx1 depletion in MPCs decreases cell growth, supporting Runx1 contribution to cell expansion. The highest Runx1 levels in SZC of normal cartilage suggest a function that supports the unique phenotype of articular chondrocytes, reflected by upregulation under conditions of compression. We propose Runx1 co-expression with Vcam1 and lubricin in murine cell clusters and human 'clones' of OA cartilage, participate in a cooperative mechanism for a compensatory anabolic function.
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Kimberly T
authors: KT
authors: LeBlanc
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Marie E
authors: ME
authors: Walcott
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Tripti
authors: T
authors: Gaur
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Shannon L
authors: SL
authors: O'Connell
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Kirti
authors: K
authors: Basil
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Christina P
authors: CP
authors: Tadiri
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: April
authors: A
authors: Mason-Savas
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Jason A
authors: JA
authors: Silva
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Janet L
authors: JL
authors: Stein
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Gary S
authors: GS
authors: Stein
authors: Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: David C
authors: DC
authors: Ayers
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.|Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Jane B
authors: JB
authors: Lian
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts.|Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Paul J
authors: PJ
authors: Fanning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit