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Updated: Jul 15, 2026
A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling
Published on: May 21, 2020
Assessing osteolysis with use of high-throughput protein chips
Arun S Shanbhag1, Adam M Kaufman, Koichiro Hayata
1Biomaterials Laboratory, Massachusetts General Hospital, GRJ 1115, 55 Fruit Street, Boston, MA 02114, USA. shanbhag@helix.mgh.harvard.edu
Background:
Previous studies of bone resorption around failed joint replacements have focused on a limited number of cytokines, primarily tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, with use of enzyme-linked immunosorbent assay and immunohistochemistry techniques. In this study, we utilized high-throughput protein chips to profile twenty-nine inflammatory cytokines around failed total joint replacements.
Methods:
Peri-implant granulomatous tissues were harvested from around the failed total hip prostheses of thirteen patients. Synovial lining capsular tissues from thirteen patients with end-stage degenerative joint disease were used as controls. After homogenization, twenty-nine cytokines were quantified with use of high-throughput protein chips.
Results:
IL-6 and IL-8 were found consistently in failed joint replacement tissues, reaffirming their prominent role in osteoclastogenesis and end-stage bone resorption. High levels of interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (MIG), both chemoattractants of activated Th1 lymphocytes, were also detected. Soluble intercellular adhesion molecule (sICAM) and transforming growth factor-beta1 (TGF-beta(1)) were not detected universally, nor were TNF-alpha or IL-1. After a twenty-four-hour organ culture, IL-1beta levels increased substantially along with those of other mediators. We measured but did not detect any activators of cytotoxic T-cells, antibody-producing Bcells, or eosinophils involved in delayed-type hypersensitivity. Variations from patient to patient were seen across all cytokines and highlight the unique response of individual patients to their joint replacements.
Conclusions:
In failed total joint replacements in patients with end-stage osteolysis, IL-6 and IL-8 may be the primary drivers of osteoclastogenesis. The presence of IP-10 and MIG imply a role for T-cells, while TGF-beta(1) and sICAM may represent a systemic attempt to modulate the inflammation. TNF-alpha and IL-1 do not appear to play a major role in the end stages of the disease.
