Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow.

Valerie A. Siclari, J. Zhu, Kentaro Akiyama, Fei Liu, Xianrong Zhang, Abhishek Chandra, Hyun Duck Nah, Songtao Shi, Ling Qin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method isolates only mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express common mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared with their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared with young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies.

Original languageEnglish
Pages (from-to)575-586
Number of pages12
JournalBone
Volume53
Issue number2
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

Fingerprint

Bone Marrow
Bone and Bones
Mesenchymal Stromal Cells
Osteogenesis
Parathyroid Hormone
Diaphyses
Immunosuppressive Agents
Inflammatory Bowel Diseases
Digestion
Cell Cycle
Injections
Cancellous Bone
Therapeutics

Keywords

  • Aging
  • Endosteal bone marrow
  • Immunosuppression
  • Mesenchymal progenitors
  • Parathyroid hormone

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Medicine(all)

Cite this

Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow. / Siclari, Valerie A.; Zhu, J.; Akiyama, Kentaro; Liu, Fei; Zhang, Xianrong; Chandra, Abhishek; Nah, Hyun Duck; Shi, Songtao; Qin, Ling.

In: Bone, Vol. 53, No. 2, 04.2013, p. 575-586.

Research output: Contribution to journalArticle

Siclari, Valerie A. ; Zhu, J. ; Akiyama, Kentaro ; Liu, Fei ; Zhang, Xianrong ; Chandra, Abhishek ; Nah, Hyun Duck ; Shi, Songtao ; Qin, Ling. / Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow. In: Bone. 2013 ; Vol. 53, No. 2. pp. 575-586.
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