Subchondral bone angiogenesis and neovascularization of the articular cartilage are features known to develop at an early stage during osteoarthritis (OA), but the exact mechanisms behind these processes have been unclear. A new study has uncovered a role for platelet-derived growth factor (PDGF)-BB in subchondral bone angiogenesis and in the development of OA in mice.

“Our study provides the first evidence that PDGF-BB derived from preosteoclasts is a key promoter of pathological subchondral bone angiogenesis during OA development,” states corresponding author Mei Wan.

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To assess the role of PDGF-BB in disease, Wan and colleagues used the destabilization of the medial meniscus (DMM) model of OA. “In mice after joint destabilization, mononuclear preosteoclasts in the subchondral bone secreted excessive amounts of PDGF-BB, which activated PDGF receptor-β signalling in pericytes for neovessel formation,” explains Wan.

The researchers used conditional PDGF-BB-knockout and transgenic mice that either lacked or overexpressed Pdgfb in osteoclast lineage cells. In this way, they could specifically assess the role of PDGF-BB production by preosteoclasts. “By using conditional PDGF-BB-knockout mice and conditional PDGF-BB transgenic mice, we found that PDGF-BB derived from preosteoclasts is both sufficient and necessary for the development of subchondral bone angiogenesis and subsequent joint degeneration,” says Wan.

conditional PDGF-BB transgenic mice spontaneously developed OA-like disease

Conditional PDGF-BB-knockout mice had reduced subchondral bone angiogenesis compared with wild-type mice following DMM and developed less severe disease than sham-operated mice. Interestingly, the conditional PDGF-BB transgenic mice spontaneously developed OA-like disease. “Our transgenic mice can serve as an ideal spontaneous OA model that should help investigators study the pathogenesis of joint degeneration and OA pain, develop early interventions and test the efficacy of new treatments for human OA,” suggests Wan.