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

Abstract

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...

Interactions between Serum Adipokines and Osteocalcin in Older Patients with Hip Fracture

“…Our results are also supported by a strong inverse association between serum leptin levels and nontraumatic fracture risk even in normal weight subjects [21], as well as the data that leptin enhances osteoblastogenesis in vitro [7, 48, 53], exerts a positive effect in fetal bone formation [54] and reduces bone loss in ovariectomized rats [55]. …”

Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin

“…The osteogenic differences between osteoarthritic and osteoporotic BMSCs can be diminished by treatment with leptin, because it might upregulate the expression of osteoprotegerin in osteoporotic BMSCs (Zhang et al 2009). This finding suggests a mechanism by which leptin promotes osteogenesis in individuals with osteoporosis.…”

“…An alternation in bone-formation capacity and reduction in the osteogenic potential of BMSCs might be one of the main reasons for osteoporosis (Perinpanayagam et al 2001;Zhang et al 2009). The biological behavior of BMSCs, such as proliferation and differentiation, could potentially be regulated by intrinsic and extrinsic factors (Koshihara et al 2003;Meyers et al 2005;Sheng et al 2007), including leptin (Han et al 2010) by, for example, using the administration of recombinant proteins (Li et al 2013) and transfection to overexpress genes (Hu et al 2013).…”

Modulation of osteoblastic/odontoblastic differentiation of adult mesenchymal stem cells through gene introduction: a brief review

“…As the genes introduced directly to stem cells in gene form or added in the culture medium of in vitro experiment in recombinant protein form or their protein product, the following were researched: Akt 6, adenosine monophosphate kinase ( AMPK )7, bone morphogenetic protein ( BMP )5,8-16, BMP2 and Runt-related transcription factor 2 ( RUNX2 )17, BMP6/7 and vascular endothelial growth factor 165 ( VEGF165 )18-20, connective tissue growth factor ( CTGF )21, dentin sialophosphoprotein ( DSPP )22, fibroblast growth factor 2 ( FGF2 ) or fibroblast growth factor receptor 2 ( FGFR2 )23-26, FHL2 (member of the LIM-only subclass of the LIM protein superfamily)27, growth and differentiation factor 5 ( GDF5 )28, growth arrest-specific gene 7b ( GAS7b )29, sonic hedgehog ( Shh )30, Hey1 31, interleukin-3 ( IL-3 )32, leptin33,34, LIM domain mineralization proteins ( LMPs )35-37, neuronal membrane glycoprotein gene ( GPM6B )38, noggin 39, oncostatin M ( OSM )40, osterix ( Osx )41, sirtuin 1 ( SIRT1 )42, retinoic acid-related orphan receptor-α ( ROR-α )43, Runx2 44, transforming growth factor β ( Tgf-β )45, tumor necrosis factor-α ( TNF-α )46-49, Twist1 50, and wingless-type MMTV integration site family ( WNT ) 5a 51 (Table 1). To express these genes, the following mesenchymal cells were used: BMSCc derived from mouse, rat, rabbit, horse, and human; ADSCs derived from human and mouse, and; DPSCs, PDLSCs, DFPCs, and DPCs derived from human and mouse.…”