美国圣地牙哥的诺华研究基金会基因体中心，发现一种称作Kartogenin分子，可以促进间叶干细胞分化成软骨细胞。经由小鼠的动物实验证实，注射Kartogenin可以改善因关节炎引起的软骨损伤，重获关节功能且无疼痛感。这项治疗退化性关节炎--骨关节炎(osteoarthritis；OA)的新发现，刊登于4月份科学期刊<Science>。

 

软骨含有间叶干细胞，能分化成软骨细胞(chondrocytes)形成结缔组织。因受伤或长期使用关节而罹患骨关节炎(最常见的关节炎)的病患，其软骨受到严重破坏，Kartogenin能促进间叶干细胞的分化，为软骨修复的重要步骤。

 

参与这项研究的主要作者- 诺华研究基金会基因体中心的分子生物学家Kristen Johnson，与研究团队共同筛选软骨中22000个分子，发现诱导间叶干细胞分化成软骨细胞的Kartogenin。在患有类似骨关节炎的小鼠实验证实，该分子可以启动蛋白聚糖(aggrecan)和胶原蛋白II(collagen II)基因表现，降低发炎物质-软骨低聚基质蛋白(cartilage oligomeric matrix protein)含量，使小鼠受损膝关节能在42天内重获承重能力。另外，kartogenin可以抑制间叶干细胞中的细丝蛋白A(filamin A)，促使间叶干细胞分化成软骨细胞，保护并修复受损软骨。 

 

 

许多人到老年时期会发生骨关节炎，然而透过外科手术清除受损软骨的成功率有限，此外，以手术促进骨末端纤维状软骨增生，又因失去自然软骨帽而成功率不高。软骨再生已经成为整形外科医学的主要目标，而这项研究带来重大的意义。

A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows. And treatment with kartogenin allowed many mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain.

The findings provide new clues in the long-running effort to find ways to regenerate cartilage, a central puzzle in the battle against osteoarthritis, scientists report online April 5 in Science.

The new approach taps into mesenchymal stem cells, which naturally reside in cartilage and give rise to cells that make connective tissue. These include chondrocytes, the only cells in the body that manufacture cartilage. Kartogenin steers the stem cells to wake up and take on cartilage-making duties. This is an essential step in the cartilage repair that falls behind in people with osteoarthritis, the most common kind of arthritis, which develops from injury or long-term joint use.

Johnson and her colleagues screened 22,000 compounds in cartilage and found that one, kartogenin, induced stem cells to take on the characteristics of chondrocytes. The molecule turned on genes that make cartilage components called aggrecan and collagen II. Tests of mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity. Kartogenin also enabled mice with knee injuries to regain weight-bearing capacity on the joint within 42 days.

Lab work revealed that kartogenin inhibits a protein called filamin A in the mesenchymal stem cells. This unleashes other compounds that can then orchestrate the activity of genes useful in turning the stem cells into functional chondrocytes. In so doing, Johnson says, kartogenin seems to protect and repair cartilage.

Millions of people develop osteoarthritis as they reach old age. Cartilage serves as the shock absorber of the skeleton, but surgery to clean out torn cartilage has limited success, as does surgery to induce growth of a fibrous kind of coating at the ends of bones that have lost their natural cartilage caps. This losing battle leaves bone-on-bone friction, inflammation and pain.

Source from http://www.sciencenews.org/view/generic/id/339669/title/Stem_cell_treatment_spurs_cartilage_growth