Review Question - QID 4477

Of the options provided, IL-1 is most associated with macrophage induced osteolysis surrounding orthopaedic implants.

Macrophages initiate the inflammatory cascade associated with aseptic loosening of orthopaedic implants by secreting platelet-derived growth factor (PDGF), prostaglandin E2 (PGE2), TNF-alpha, IL-1, and IL-6.

Archibeck et al. state the primary cells involved in the process of periprosthetic loosening include the macrophage, osteoblast, fibroblast, and osteoclast. They report the chemical mediators that are responsible for the cellular interactions and effects on bone primarily include PGE2, TNF-alpha, IL-1, and IL-6.

Drees et al. discuss the molecular pathway of aseptic loosening of orthopedic implants. They describe the following steps: 1) Wear debris particles released at the cement–bone interface attract macrophages, which, in turn, are stimulated to produce proinflammatory mediators and proteolytic enzymes; 2) RANKL, TNF-alpha, IL-1, IL-6, IL-17, and M-CSF mediate the differentiation of myeloid precursor cells into multinucleated osteoclasts, which release cathepsin K and acid and cause resorption lacunae; 3) Mesenchymal cells (prosthesis-loosening fibroblasts) present at the bone surface contribute actively to bone resorption.

Illustration A shows the pathway described by Drees et al.

Incorrect Answers
Answer 1: BMP-2,4,6, and 7 all exhibit osteoinductive activity but BMP-3 does not.
Answer 2: IL-10 inhibits osteoclast formation along with calcitonin
Answer 3: SOX-9 is a key transcription factor involved in the differentiation of cells towards the cartilage lineage
Answer 4: Osteoprotegrin binds to RANKL on the osteoblast, preventing RANK activation and inhibiting osteoclast activity.