- 期刊
- OpenAccess
The Pathophysiologic Effects of Growth Factors, Cytokines, and Bone Morphogenetic Proteins in the Growth and Development of Skeletal Tissues
生長激素、細胞動力素及骨成形蛋白在骨骼組織的生長發育中所俱有之病理生理功能
摘要
在人類的骨骼系統中，骨再塑造作用是持續不斷的存在。這些維持骨骼系統的細胞參與兩類作用：將骨質除去的骨吸收及負責骨質增加的骨形成。骨骼組織中存在著各種的生長激素，它們在生長及成熟的骨骼中具有調節骨骼代謝的作用。此外，生長激素也在骨折修補的同化過程中扮演重要的角色。胜類生長激素是一種能與特定細胞膜受體結合，而刺激細胞增生的蛋白質。低濃度的血小板生長激素能經由增加局部產生前列腺素E2而刺激骨吸收，它亦能在慢性發炎過程中刺激前列腺素I2的合成而引發或加速骨質溶解病變。上皮生長激素也是經由增加局部產生前列腺素E2而刺激骨吸收。骨骼中含有成纖維細胞生長激素，它或許實際參與局部骨形成的調節作用，在體外培養皿中類造骨細胞是成纖維細胞的靶細胞，且骨細胞能合成成纖維細胞生長激素。類胰島生長激素是被骨細胞合成，然後儲存在骨基質中，它能刺激骨細胞合成去氧核醣核酸及第一類膠原纖維。變形生長激素在骨骼及血小板中相當豐富，它能在體內促進傷口癒合，同時也能刺激成纖維細胞及成骨細胞產生細胞外基質蛋白。幹細胞因子是一個最新發現的造血生長因子，它俱有刺激形成類蝕骨多核細胞的能力。介白質（IL-1 alpha, IL-1 beta）及腫瘤壞死因子在骨代謝中所扮演的角色皆為抑制性作用，IL-1 beta的效力大於IL-1 alpha、再大於腫瘤生長因子。細胞動力素與骨生長因子在成骨細胞中的交互作用，很可能在骨基質的局部發炎區扮演非常重要的角色。骨成形蛋白存在於骨基質中，它可以作用在未成熟的間葉細胞，經由軟骨內的骨分化作用達到骨骼誘發的功能。另外，尚有一些其他的因子存在於骨基質中，俱有類以骨成形蛋白的活性，包括骨誘導因子、成骨因子、活化因子及軟骨誘導因子。結論，這些發現皆能証明胜類生長激素、細胞動力素及骨成形蛋白，皆在骨骼組織的生長與發育中，俱有某種重要的病理功能。
並列摘要
In humans, the skeleton is constantly remodeling. The cells involved in maintaining the skeleton fall into two categories: those responsible for the removal of bone (bone resorption) and those responsible for bone formation. Skeletal tissue is known to contain various growth factors. Growth factors are thought to regulate bone turnover in growing and mature skeletal tissue. In addition, growth factors may participate in the anabolic processes involved in fracture repair. Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Low concentrations of platelet-derived growth factor (PDGF) stimulate bone resorption via the enhanced local production of PGE2, and it can also stimulate PGI2 synthesis in chronic inflammatory processes to elicit or accelerate osteolysis. Epidermal growth factor (EGF) stimulates bone resorption also by a mechanism that involves the enhanced local production of PGE2. Fibroblast growth factor (FGF) may be involved in the local regulation of bone formation; FGF is present in bone, osteoblast-like bone cells are target cells for FGF in cultures, and bone cells synthesize FGF-line molecules in cultures. Insulin-like growth factors (IGF-I and IGF-II) are produced by bone cells and are stored in the bone matrix, and stimulate bone cell DNA synthesis and type I collagen production. Transforming growth factor-beta (TGF-beta) is abundant in bones and platelets, promotes wound healing in vivo, and is a potent stimulator of the production of extracellular matrix proteins in fibroblasts. Stem cell factor (SCF) is a newly described hematopoietic growth factor that has the capacity to stimulate the formation of osteoclast-like multinucleated cells. The effect of cytokines IL-1 alpha, IL-1 beta, and TNF on bone metabolism are profoundly inhibitory, with the rank order of potency IL-1 beta greater than IL-1 alpha and greater than TNF. The interaction of cytokines and bone growth factors with osteoblasts are likely to be of critical importance in the regulation of bone mass at local inflammatory sites. Bone morphogenetic protein (BMP) exists in the bone matrix and acts on immature mesenchymal cells to initiate bone induction through endochondral bone differentiation. Other factors that have been reported to be present in the bone matrix and have BMP-like activity include osteoinductive factor (OIF), osteogenin, active, and cartilage-inducing factor (CIF). In conclusion, these findings demonstrate that peptide growth factors, cytokines, and bone morphogenetic proteins may all otain certain important pathophysiologic effects in the growth and development of skeletal tissues.