The interaction of MMP-2/B7-H3 in human osteoporosis

- MMP-2 was positively correlated with sB7-H3 in osteoporosis patients.
- Elevated MMP-2 levels resulted in elevated sB7-H3 and reduced osteoblastic mB7-H3.
- B7-H3-deficient MG63 cells decreased osteoblastic markers and mineralized nodules.
- Membrane B7-H3 is required for the later phases of osteoblast differentiation.
- MMP-2/B7-H3 plays a negative regulatory role in osteoporosis.

The immune costimulatory molecule B7-H3 has been shown to be involved in the regulation of murine bone formation. However, the role of B7-H3 in bone metabolic diseases remains unknown. In our study, matrix metalloproteinase 2 (MMP-2) and soluble B7-H3 (sB7-H3) were found to be correlatively up-regulated in the sera of osteoporosis patients. Furthermore, our results showed that MG63 cells treated with MMP-2 inhibitors produced lower amounts of sB7-H3 while cells with recombinant MMP-2 had an increased membrane B7-H3 (mB7-H3) shedding. Therefore, elevated MMP-2 levels resulted in an elevation of serum sB7-H3 and reduction of osteoblastic mB7-H3. B7-H3 knockdown in MG63 cells significantly decreased osteoblastic markers and substantially decreased the number of mineralized nodules after 21 days. Thus, B7-H3-deficient MG63 cells exhibited impaired bone formation. These results suggest that mB7-H3 is required for the later phases of osteoblast differentiation and that MMP-2/B7-H3 plays a negative regulatory role in osteoporosis.