Research Area

Osteoprogenitor


Introduction and Function of Osteoprogenitor

Osteoprogenitor

Osteoprogenitor cells, also known as osteoblasts, are named for their ability to self-sustain and self-renew. Stem cells can be divided into two stem cells or two directed progenitor cells by a high degree of the regulation mechanism. The cell renewal is accurate, and the stem cells are relatively static during the whole proliferation process. The cell completes the task of DNA synthesis and cell expansion and retains its original genetic information, while continuously producing progenitor cells, it does not proliferate or differentiate itself. It can differentiate into osteoblasts under the induction of culture medium containing dexamethasone, ascorbic acid, and glycerol phosphate. In the process of differentiation, characteristic bone cell characteristics can emerge: synthesis of type I collagen, expression of alkaline phosphatase, secretion of bone calcium and hydroxyapatite deposition. In the current bone tissue engineering studies, there are many reports on osteogenic cells, and there are relatively few studies on osteoprogenitor cells that can proliferate, differentiate into osteogenic cells and eventually form bone. By understanding the biological characteristics of the progenitor cells and some relatively new research progress, we can provide some new ideas and ways in the treatment of defect repair or osteoporosis of bone tissue.

Features of Osteoprogenitor

Characteristics of the differentiation stage of osteoprogenitor cells: Osteoblasts derived from mesenchymal osteoprogenitor cells and play a major role in osteogenesis. When these cells are introduced into the bone defect area of adult animals, they can promote bone formation, so it is clear the function and differentiation process of osteoprogenitors allows us to have a deeper understanding of the metabolism of bone tissue. It has been reported that bone progenitor cells are obtained by digesting the fetal rat skull with timed and continuous enzymes. Osteoprogenitor cells are highly sensitive to dexamethasone and the expression of bone formation markers is enhanced under the induction of dexamethasone. It was confirmed by the test of alkaline phosphatase activity and calcium deposition that the first to third generations of enzyme-digested fetal rat skull cells responded well to dexamethasone. This indicates that they are osteoprogenitors located on the periosteum and bone surface and immature osteoblasts. The third generation of cells can form the largest number of bone nodules, indicating that this is the largest number of osteoprogenitor cells. The first generation is the most proliferative osteoprogenitor cell. Conversely, the fourth-generation enzyme digestion of fetal rat skull cells has a poor response to dexamethasone. The experiment shows that the expression of glucocorticoid receptor in bone cells is lower than that of osteoprogenitor cells and osteoblasts, indicating the fourth and fifth generations of enzymes digestive fetal rat skull cells mainly include bone cells. Age-related changes in osteoprogenitor cells: In studies of age-related changes in osteoblasts, it was found that the bone-forming ability of human bone marrow stromal cells was not related to age. The number of stromal cells in the elderly and young adults is basically similar in terms of in vitro culture. The reduced bone formation capacity of the elderly is due to changes in the internal environment of the individual that reduce the osteogenic potential of the osteoprogenitor cells. With the increase of age, the proliferative capacity of osteoprogenitor cells gradually weakened, but the number did not decrease significantly. Osteoprogenitor cells in aged mice are less sensitive to mitogenic results induced by basic fibroblast growth factor than young rats.

Regulation of Osteoprogenitor

As osteoprogenitor cells play an important role in bone formation, the regulation of osteoprogenitor cells is particularly important. Y-neuropeptide type 2 receptors on osteoprogenitor cells: Traditionally, the process of bone formation is mainly regulated by the endocrine system and local factors such as cytokines and growth factors. However, this view is gradually changing. There is increasing evidence that neuro cytokines in bone tissue can also alter bone cell activity. Studies have confirmed that nerve cells entering the bone tissue are associated with the hypothalamus, which is consistent with the conditional deletion of the Y-neuropeptide type 2 receptors. Y neuropeptide immunoreactive fibers have been shown to be present in bone marrow, periosteum, and bone tissue. Studies have shown that the number of osteoprogenitor cells derived from Y2-/- mice and their osteogenic capacity is enhanced. At the same time, the lack of Y2 receptor can cause stromal cells to down-regulate the Y1 receptor, possibly because bone tissue cannot inhibit the release of Y neuropeptide feedback, which leads to excessive stimulation of Y1 receptor and promotes bone mineralization, which may be for the treatment of bone mass. Proline-rich tyrosine kinase 2 and focal adhesion kinase (FAK) are a non-receptor tyrosine protein kinase that together forms the focal adhesion kinase family. Proline-rich tyrosine kinase 2 is the highest-level kinase in the brain and hematopoietic system. Many in vitro experiments have demonstrated that proline-rich tyrosine kinase 2 regulates the function and activity of osteoclasts. Some scholars have unexpectedly found that PYK2-/- mouse bone formation has increased significantly. Consistent with this finding, the differentiation ability and activity of osteoprogenitor cells in the bone marrow of PYK2-/- mice were enhanced. Moreover, daily injection of small proline-rich tyrosine kinase 2 inhibitors in ovariectomized rats can effectively increase bone formation and reduce bone loss. It is believed that proline-rich tyrosine kinase 2 regulates differentiation of early osteoprogenitor cells, and proline-rich tyrosine kinase 2 inhibitors promote bone formation and may be used in the treatment of osteoporosis in the future. Internal fixation is a common method for the treatment of fractures, but at the same time, the internal fixation device also provides suitable parasitic space for the biofilm required for pathogen reproduction, thereby causing infection and another concurrency disease. Severe infections can delay fracture healing and stimulate bone tissue absorption. In the event of an infection, the usual treatment is to remove the internal fixation device or to change it to external fixation, which will obviously affect the healing of the fracture or cause discomfort to the patient. Human recombination of bone protein-1 (rhOP-1, also known as BMP7) has been shown to induce new bone formation in critical size bone defects in mice with acute infection. Some scholars have found through experiments that the use of bone morphogenetic protein injection can promote bone formation if chronic infection occurs after fixation within the fracture, and antibiotic treatment can enhance the process. Bone morphogenetic protein can effectively promote the proliferation and differentiation of osteoprogenitor cells and express osteoblast markers. Osteoprogenitor cells have been reported in the perichondrium. These osteoprogenitor cells up-regulate bone morphogenetic protein 2 during differentiation into mature osteoblasts that produce a bone matrix, and bone morphogenetic protein 2 itself is a potent inducer of osteogenesis. Effect of the extracorporeal shock wave on osteoprogenitor cells: Extracorporeal shock wave has been used in the treatment of kidney stones for more than 20 years. In recent years, shock waves have been applied to the treatment of fracture healing. At present, most scholars believe that the osteogenesis of shock waves is caused by promoting the expression of one or several cytokines. Wang et al. studied the effects of shock waves on bone marrow mesenchymal progenitor cells. In this study, bone marrow stroma and hematopoietic cells were collected to assess the impact of shock waves on the rat femur, forming colony progenitor cells (CFU-F and CFU-O), granulocytes, red blood cells, monocytes, and megakaryocytes. At the same time, the alkaline phosphatase activity and the amount of transforming growth factor β1 produced in the cultured bone marrow stromal cells were measured. The results show that the most ideal shock wave parameter is 500 pulses, 0.06 mg/mm2, which can better promote the growth of CFU2F and CFU2O. Alkaline phosphatase activity was increased by 1173 times with P2 nitrophenol. The experiment also found that the shock wave was enhanced by the energy density of 0.16 mg/mm2, the dose of 500, and the expression of transforming growth factor β1 was strengthened. After 12 days, the osteoprogenitor cells formed colonies, which confirmed that transforming growth factor β1 promoted bone marrow stromal cells in the shock wave. It plays an important role in the transformation of osteoprogenitor cells. Therefore, the biological effects of shock waves on osteoprogenitor cells and bone formation have been studied. The role of gap junctions between endothelial cells and osteoprogenitor cells in osteogenesis has been demonstrated to be a coupled process of angiogenesis and bone tissue development and maturation. The close relationship between vascular endothelium and osteoblasts and osteoblasts suggests that endothelial cells (ECs) play an important role in regulating bone formation and function. Some scholars have found that the gap junction between endothelial cells and osteoprogenitor cells is a key factor in enhancing the osteogenic activity of osteoprogenitor cells. On this basis, other scholars have proposed that endothelial cells can express bone morphogenetic protein 2 and enhance the osteogenic ability of osteoprogenitor cells. This effect requires a director tight connection between endothelial cells and osteoprogenitor cells. Many times, the formation of new bone is limited by the lack of blood vessels in the tissue. To solve this problem, researchers hope to promote angiogenesis by using angiogenic factors. There have been no reports of tissue engineering bone formation by endothelial cell transplantation, the impact of this complex interaction between endothelial cells and osteoprogenitor cells on osteogenesis deserves further investigation.

References:

  1. Ibrahim A, Bulstrode N W, Whitaker I S, et al. Nanotechnology for Stimulating Osteoprogenitor Differentiation. Open Orthopaedics Journal. 2016, 10(Suppl-3, M5):849.
  2. Goodman S B, Hwang K L. Treatment of Secondary Osteonecrosis of the Knee With Local Debridement and Osteoprogenitor Cell Grafting. Journal of Arthroplasty. 2015, 30(11):1892-1896.
  3. Park J, Gebhardt M, Golovchenko S, et al. Dual pathways to endochondral osteoblasts: a novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage. Biology Open. 2015, 4(5):608-621.
  4. Pikilidou M, Yavropoulou M, Antoniou M, et al. The Contribution of Osteoprogenitor Cells to Arterial Stiffness and Hypertension. Journal of Vascular Research. 2015, 52(1):32.
  5. Dogaki Y, Lee S Y, Niikura T, et al. Efficient derivation of osteoprogenitor cells from induced pluripotent stem cells for bone regeneration. International Orthopaedics. 2014, 38(9):1779-1785.

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