Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics

Rodríguez, Juan ́Pablo; Garat, Solange; Gajardo, H; Pino, A M; Seitz, G

doi:10.1002/(sici)1097-4644(19991201)75:3<414::aid-jcb7>3.3.co;2-3

Cited by 91 publications

(93 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on these properties, HTRA1 may be deemed as a key factor in determining the outcome of diseases such as age-related osteoporosis, where impaired BMSC osteogenesis and upregulated adipogenesis is believed to be a major contributor to the underlying pathology [24,49].…”

Section: Discussionmentioning

confidence: 99%

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

et al. 2012

View full text Add to dashboard Cite

Mammalian high-temperature requirement serine protease A1 (HTRA1) is a secreted member of the trypsin family of serine proteases which can degrade a variety of bone matrix proteins and as such has been implicated in musculoskeletal development. In this study, we have investigated the role of HTRA1 in mesenchymal stem cell (MSC) osteogenesis and suggest a potential mechanism through which it controls matrix mineralization by differentiating boneforming cells. Osteogenic induction resulted in a significant elevation in the expression and secretion of HTRA1 in MSCs isolated from human bone marrow-derived MSCs (hBMSCs), mouse adipose-derived stromal cells (mASCs), and mouse embryonic stem cells. Recombinant HTRA1 enhanced the osteogenesis of hBMSCs as evidenced by significant changes in several osteogenic markers including integrin-binding sialoprotein (IBSP), bone morphogenetic protein 5 (BMP5), and sclerostin, and promoted matrix mineralization in differentiating boneforming osteoblasts. These stimulatory effects were not observed with proteolytically inactive HTRA1 and were abolished by small interfering RNA against HTRA1. Moreover, loss of HTRA1 function resulted in enhanced adipogenesis of hBMSCs. HTRA1 Immunofluorescence studies showed colocalization of HTRA1 with IBSP protein in osteogenic mASC spheroid cultures and was confirmed as being a newly identified HTRA1 substrate in cell cultures and in proteolytic enzyme assays. A role for HTRA1 in bone regeneration in vivo was also alluded to in bone fracture repair studies where HTRA1 was found localized predominantly to areas of new bone formation in association with IBSP. These data therefore implicate HTRA1 as having a central role in osteogenesis through modification of proteins within the extracellular matrix. STEM CELLS

show abstract

Section: Discussionmentioning

confidence: 99%

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Although MSCs from OA patients responded to osteogenic induction with an upregulated level in gene and protein product expression, these differences between OA and OP groups were diminished after treatment with leptin. Rodríguez et al 26 observed that osteoporotic cells exhibited a lower proliferation rate than ''normal'' control cells. In our study, cell growth curve showed that similar proliferation status in OA and OP patients.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic potential and responsiveness to leptin of mesenchymal stem cells between postmenopausal women with osteoarthritis and osteoporosis

Zhang

Jiang

et al. 2009

Journal Orthopaedic Research

View full text Add to dashboard Cite

The aim of this study was to compare the osteogenic potential and responsiveness to leptin of mesenchymal stem cells (MSCs) from bone marrow between postmenopausal women with osteoarthritis (OA) and osteoporosis (OP). MSCs of the proximal femur from OA and OP donors were cultured under control and different experimental mediums. After verifying the availability of primary cells, their osteogenic potential and responsiveness to leptin were compared between two groups. Similar patterns of cell growth were shown in both OA and OP groups. However, after the sixth passage, the viability of undifferentiated cells decreased more in OP than in OA donors. Under the same osteogenic supplements condition, the mRNA expression of osteogenesis-specific genes, osteocalcin (OC) and alkaline phosphatase (ALP) were higher in OA group. Comparison of bone matrix mineralization was parallel to that of mRNA expression. The level of bone-specific ALP (BAP) was higher in cells from donors with OA, whereas osteoprotegerin (OPG) was higher in OP group. This difference in BAP expression proved to be insignificant after the administration of leptin. Although leptin upregulated the expression of OPG, a significant difference still existed between OA and OP. In conclusion, differential osteogenic potential and responsiveness to leptin of MSCs were noted between postmenopausal women with OA and OP. Differential biological behavior of MSCs seems to be partly related to the different distribution of bone mass between OA and OP populations. Keywords: mesenchymal stem cells; bone formation; osteoarthritis; osteoporosis; leptin Osteoarthritis (OA) and osteoporosis (OP) are two common diseases which affect the life quality of aged people. Although OA is traditionally regarded as a disease of articular cartilage with main features of cartilage degeneration and erosion, the roles of the underlying subchondral bone in the etiology of OA has been debated for many years. 1-4 OP is universally accepted to be a systemic disease characterized as susceptibility to fractures, bone loss, and fragile trabecular architecture. The imbalance between bone formation and resorption, due to genetic, hormonal, and other unknown causes, is considered to bring about the result of OP. Although both of them are related to bone metabolism, a clearly defined relationship between OA and OP has not been interpreted. Dequeker et al. 5 pointed out an inverse relationship between OA and OP. Also, primary OA and OP rarely coexist in the same patient clinically. 6,7 Bone mineralization is influenced by the functions of osteoblasts, osteoclasts, and mesenchymal stem cells (MSCs). Studies in bone mineral density (BMD) measurement showed that patients with OA had higher BMD at both axial and peripheral sites than both normal subjects and patients with OP. [8][9][10][11][12][13] It remains unknown whether differential biological behavior of those bone cells leads to differential distribution of bone mass between OA and OP populations. However, up to now, the role of bone MSC...

show abstract

“…However, age-dependent changes in the population of osteoprogenitor cells are discussed controversially. Recent results have given evidence of aging in marrow stromal progenitor cells [10,[40][41][42][43][44][45][46]. Other reports demonstrated that osteogenic progenitor cells were maintained during aging [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Fetal bone cells for tissue engineering

Montjovent

Burri

Mark

et al. 2004

Bone

View full text Add to dashboard Cite

We envision the use of human fetal bone cells for engineered regeneration of adult skeletal tissue. A description of their cellular function is then necessary. To our knowledge, there is no description of human primary fetal bone cells treated with differentiation factors. The characterization of fetal bone cells is particularly important as the pattern of secreted proteins from osteoblasts has been shown to change during aging. In the first part of this work, human primary fetal bone cells were compared to adult bone cells and mesenchymal stem cells for their ability to proliferate and to differentiate into osteoblasts in vitro. Cell proliferation, gene expression of bone markers, alkaline phosphatase (ALP) activity, and mineralization were analyzed during a time-course study. In the second part of this paper, bone fetal cells behavior exposed to osteogenic factors is further detailed. The doubling time of fetal bone cells was comparable to mesenchymal stem cells but significantly shorter than for adult bone cells. Gene expression of cbfa-1, ALP, a1 chain of type I collagen, and osteocalcin were upregulated in fetal bone cells after 12 days of treatment, with higher inductions than for adult and mesenchymal stem cells. The increase of ALP enzymatic activity was stronger for fetal than for adult bone cells reaching a maximum at day 10, but lower than for mesenchymal stem cells. Importantly, the mineralization process of bone fetal cells started earlier than adult bone and mesenchymal stem cells. Proliferation of fetal and adult bone cells was increased by dexamethasone, whereas 1a,25-dihydroxyvitamin D 3 did not show any proliferative effect. Mineralization studies clearly demonstrated the presence of calcium deposits in the extracellular matrix of fetal bone cells. Nodule formation and calcification were strongly increased by the differentiation treatment, especially by dexamethasone. This study shows for the first time that human primary fetal bone cells could be of great interest for bone research, due to their fast growth rate and their ability to differentiate into mature osteoblasts. They represent an interesting and promising potential for therapeutic use in bone tissue engineering.

show abstract

Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics

Cited by 91 publications

References 24 publications

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

Osteogenic potential and responsiveness to leptin of mesenchymal stem cells between postmenopausal women with osteoarthritis and osteoporosis

Fetal bone cells for tissue engineering

Contact Info

Product

Resources

About