Oreffo R O, Bonewald L, Kukita A, Garrett I R, Seyedin S M, Rosen D, Mundy G R
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
Endocrinology. 1990 Jun;126(6):3069-75. doi: 10.1210/endo-126-6-3069.
Demineralized bone matrix contains a number of growth factors for osteoblast-like cells. Two of these, the novel glycoprotein osteoinductive factor (OIF) and transforming growth factor-beta (TGF beta), act together to cause ectopic bone formation in vivo. Since OIF, like TGF beta, is likely released from bone when the matrix is resorbed, we examined the effects of homogeneous OIF and TGF beta on osteoclast function. Osteoclast function was tested in isolated avian osteoclasts and was measured in terms of tartrate-resistant acid phosphatase (TRAP) activity, oxygen-derived free radical production, and formation of characteristic resorption lacunae on slices of sperm whale dentine. OIF (50-100 ng/ml) inhibited the capacity of these osteoclasts to form lacunae whether assessed by the number of excavations per slice or by the total area resorbed. OIF (10-100 ng/ml) or TGF beta (10-20 ng/ml) caused a decrease in TRAP activity as well as a reduction in oxygen-derived free radical generation detected by nitroblue tetrazolium staining. TGF beta had no effect on the resorption capacity of isolated osteoclasts in concentrations that inhibited TRAP activity and nitroblue tetrazolium staining. These results suggest that growth regulatory factors, such as OIF and TGF beta, released during the resorption of bone may be endogenous inhibitors of continued osteoclastic activity. This cessation of osteoclast activity may be an essential preliminary step to the new bone formation that occurs at resorption sites during bone remodeling.
脱矿骨基质含有多种促进成骨样细胞生长的因子。其中两种，即新型糖蛋白骨诱导因子（OIF）和转化生长因子-β（TGF-β），共同作用可在体内诱导异位骨形成。由于OIF与TGF-β一样，可能在基质吸收时从骨中释放出来，因此我们研究了纯化的OIF和TGF-β对破骨细胞功能的影响。在分离的禽破骨细胞中检测破骨细胞功能，并通过抗酒石酸酸性磷酸酶（TRAP）活性、氧衍生自由基的产生以及在抹香鲸牙本质切片上形成特征性吸收陷窝来进行测定。OIF（50 - 100 ng/ml）抑制这些破骨细胞形成陷窝的能力，无论是通过每片切片上的侵蚀数量还是通过吸收的总面积来评估。OIF（10 - 100 ng/ml）或TGF-β（10 - 20 ng/ml）导致TRAP活性降低，同时通过硝基蓝四唑染色检测到氧衍生自由基生成减少。在抑制TRAP活性和硝基蓝四唑染色的浓度下，TGF-β对分离的破骨细胞的吸收能力没有影响。这些结果表明，在骨吸收过程中释放的生长调节因子，如OIF和TGF-β，可能是持续破骨细胞活性的内源性抑制剂。破骨细胞活性的停止可能是骨重塑过程中在吸收部位发生新骨形成的一个重要前期步骤。
