Clinical Orthopaedics and Related Research®

, Volume 470, Issue 9, pp 2528–2540 | Cite as

Immune and Inflammatory Pathways are Involved in Inherent Bone Marrow Ossification

  • Umut Atakan GurkanEmail author
  • Ryan Golden
  • Vipuil Kishore
  • Catherine P. Riley
  • Jiri Adamec
  • Ozan AkkusEmail author
Symposium: Allograft Research and Transplantation



Bone marrow plays a key role in bone formation and healing. Although a subset of marrow explants ossifies in vitro without excipient osteoinductive factors, some explants do not undergo ossification. The disparity of outcome suggests a significant heterogeneity in marrow tissue in terms of its capacity to undergo osteogenesis.


We sought to identify: (1) proteins and signaling pathways associated with osteogenesis by contrasting the proteomes of ossified and poorly ossified marrow explants; and (2) temporal changes in proteome and signaling pathways of marrow ossification in the early and late phases of bone formation.


Explants of marrow were cultured. Media conditioned by ossified (n = 4) and poorly ossified (n = 4) subsets were collected and proteins unique to each group were identified by proteomic analysis. Proteomic data were processed to assess proteins specific to the early phase (Days 1–14) and late phase (Days 15–28) of the culture period. Pathways involved in bone marrow ossification were identified through bioinformatics.


Twenty-eight proteins were unique to ossified samples and eight were unique to poorly ossified ones. Twelve proteins were expressed during the early phase and 15 proteins were specific to the late phase. Several identified pathways corroborated those reported for bone formation in the literature. Immune and inflammatory pathways were specific to ossified samples.


The marrow explant model indicates the inflammatory and immune pathways to be an integral part of the osteogenesis process.

Clinical Relevance

These results align with the clinically reported negative effects of antiinflammatory agents on fracture healing.


Vascular Endothelial Growth Factor Notch Signaling Osteoinductive Factor Methyl Methanethiosulfonate Marrow Explants 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank David VanSickle PhD, DVM for insightful discussions on bone marrow ossification model and Pamela Lachik for help with the μCT system.

Supplementary material

11999_2012_2459_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 26 kb)
11999_2012_2459_MOESM2_ESM.docx (38 kb)
Supplementary material 2 (DOCX 38 kb)
11999_2012_2459_MOESM3_ESM.docx (19 kb)
Supplementary material 3 (DOCX 19 kb)
11999_2012_2459_MOESM4_ESM.docx (22 kb)
Supplementary material 4 (DOCX 23 kb)


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Copyright information

© The Association of Bone and Joint Surgeons® 2012

Authors and Affiliations

  • Umut Atakan Gurkan
    • 1
    Email author
  • Ryan Golden
    • 2
  • Vipuil Kishore
    • 3
  • Catherine P. Riley
    • 4
  • Jiri Adamec
    • 5
  • Ozan Akkus
    • 3
    • 6
    • 7
    Email author
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyBrigham and Women’s Hospital, Harvard Medical SchoolCambridgeUSA
  2. 2.Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteUSA
  3. 3.Department of Mechanical and Aerospace EngineeringCase Western Reserve UniversityClevelandUSA
  4. 4.Department of Research and Development Pathology AssociatesMedical LaboratoriesSpokaneUSA
  5. 5.Department of BiochemistryUniversity of Nebraska-LincolnLincolnUSA
  6. 6.Department of Biomedical EngineeringCase Western Reserve UniversityClevelandUSA
  7. 7.Department of OrthopaedicsUniversity Hospitals of ClevelandClevelandUSA

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