| 초록 |
Initial identification of osteoactivin (OA)/glycoprotein non #8208;melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post #8208;fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV #8208;promoter (OA #8208;Tg). Western blot analysis showed increased OA/gpnmb in OA #8208;Tg osteoblasts, compared to wild #8208;type (WT). In OA #8208;Tg mouse femurs versus WT littermates, micro #8208;CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA #8208;Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over #8208;expressed in osteoclasts in OA #8208;Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX #8208;1 and RANK #8208;L, and decreased osteoclast numbers in OA #8208;Tg, compared to WT mice, indicating decreased bone remodeling in OA #8208;Tg mice. The proliferation rate of OA #8208;Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA #8208;Tg osteoprogenitors. Quantitative RT #8208;PCR analysis showed increased TGF #8208; beta;1 and TGF #8208; beta; receptors I and II expression in OA #8208;Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. J. Cell. Physiol. 230: 72 ndash;83, 2016. ⓒ 2015 Wiley Periodicals, Inc. |
