Gremlin 1 Expression Distinguishes Stem Cells Able to Regenerate Bones and Cartilage in Adult Mice

A newly identified type of stem cell in the bone marrow of adult mice was found to be capable of regenerating both bone and cartilage.

Investigators at Columbia University (New York, NY, USA) reported in the January 15, 2015, online edition of the journal Cell that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defined a population of osteochondroreticular (OCR) stem cells in the bone marrow.

BMPs are considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. Deletion of gremlin 1 in mice caused increased bone formation and increased trabecular bone volume, whereas overexpression caused inhibition of bone formation and osteopenia.

The investigators found that OCR stem cells self-renewed and generated osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells were concentrated within the metaphysis of long bones not in the perisinusoidal space and were needed for bone development, bone remodeling, and fracture repair. Gremlin 1 expression also identified intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Thus, gremlin 1 expression identified distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).

"Our findings raise the possibility that drugs or other therapies can be developed to stimulate the production of OCR stem cells and improve the body's ability to repair bone injury—a process that declines significantly in old age," said senior author Dr. Timothy C. Wang, professor of medicine at Columbia University.

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