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The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs) to mechanical strain is inversely related to body mass index of the donor.

Friedl G, Windhager R, Schmidt H, Aigner R - Acta Orthop (2009)

Bottom Line: We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism.The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity.Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Orthopaedic Surgery, Medical University of Graz, Austria. gerald.friedl@medunigraz.at

ABSTRACT

Background: While the importance of physical factors in the maintenance and regeneration of bone tissue has been recognized for many years and the mechano-sensitivity of bone cells is well established, there is increasing evidence that body fat constitutes an independent risk factor for complications in bone fracture healing and aseptic loosening of implants. Although mechanical causes have been widely suggested, we hypothesized that the osteogenic mechano-response of human mesenchymal stem cells (hMSCs) may be altered in obese patients.

Methods: We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism.

Results and interpretation: The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity. Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor. Such an upstream imprinting process mediated by factors tightly related to the donor's fat metabolism, which hampers the mechanosensitivity of hMSCs in obese patients, may be of pathogenetic relevance for the complications associated with obesity that are seen in orthopedic surgery.

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Osteogenic response of hMSCs to mechanical strain. A. The phenotypic response expressed as relative change in ALP activity between unstrained (CTR) and strained (CTS) hMSCs at a culture-well based level (μM/min) accounts for both. B. The effects on cell-density and cell-based ALP activity. Dashed lines show mean values.
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Figure 0001: Osteogenic response of hMSCs to mechanical strain. A. The phenotypic response expressed as relative change in ALP activity between unstrained (CTR) and strained (CTS) hMSCs at a culture-well based level (μM/min) accounts for both. B. The effects on cell-density and cell-based ALP activity. Dashed lines show mean values.

Mentions: The early osteogenic marker genes were all significantly upregulated due to CTS: i.e. RUNX2 (1.9-fold), ALPL (2.7-fold), SPARC (4.2-fold), SPP1 (2.8-fold). COL1A1 expression was also significantly enhanced (3.5-fold), while the median value of the messages of cell cycle-related antigen Ki67 tended to be decreased (Table 3). This was accompanied by an increase in cell-based ALP activity (mean: plus 40% (SD 24); p < 0.01) (Figure 1). Cell density was lower following CTS compared with CON (mean: minus 20% (SD 15), p = 0.02; Figure 1), which was similar to the changes found in cell viability tested by XTT assay (minus 18% (SD 18), p < 0.05). As a consequence, the phenotypic osteogenic response in terms of cell-based ALP activity and cell numbers (μM/min) was not statistically significantly altered by CTS on average (mean: plus 11% (SD 29), p = 0.3), but ranged widely between minus 31% and plus 60% (Figure 1). No significant sex differences were found in any of the variables mentioned previously.


The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs) to mechanical strain is inversely related to body mass index of the donor.

Friedl G, Windhager R, Schmidt H, Aigner R - Acta Orthop (2009)

Osteogenic response of hMSCs to mechanical strain. A. The phenotypic response expressed as relative change in ALP activity between unstrained (CTR) and strained (CTS) hMSCs at a culture-well based level (μM/min) accounts for both. B. The effects on cell-density and cell-based ALP activity. Dashed lines show mean values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823184&req=5

Figure 0001: Osteogenic response of hMSCs to mechanical strain. A. The phenotypic response expressed as relative change in ALP activity between unstrained (CTR) and strained (CTS) hMSCs at a culture-well based level (μM/min) accounts for both. B. The effects on cell-density and cell-based ALP activity. Dashed lines show mean values.
Mentions: The early osteogenic marker genes were all significantly upregulated due to CTS: i.e. RUNX2 (1.9-fold), ALPL (2.7-fold), SPARC (4.2-fold), SPP1 (2.8-fold). COL1A1 expression was also significantly enhanced (3.5-fold), while the median value of the messages of cell cycle-related antigen Ki67 tended to be decreased (Table 3). This was accompanied by an increase in cell-based ALP activity (mean: plus 40% (SD 24); p < 0.01) (Figure 1). Cell density was lower following CTS compared with CON (mean: minus 20% (SD 15), p = 0.02; Figure 1), which was similar to the changes found in cell viability tested by XTT assay (minus 18% (SD 18), p < 0.05). As a consequence, the phenotypic osteogenic response in terms of cell-based ALP activity and cell numbers (μM/min) was not statistically significantly altered by CTS on average (mean: plus 11% (SD 29), p = 0.3), but ranged widely between minus 31% and plus 60% (Figure 1). No significant sex differences were found in any of the variables mentioned previously.

Bottom Line: We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism.The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity.Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Orthopaedic Surgery, Medical University of Graz, Austria. gerald.friedl@medunigraz.at

ABSTRACT

Background: While the importance of physical factors in the maintenance and regeneration of bone tissue has been recognized for many years and the mechano-sensitivity of bone cells is well established, there is increasing evidence that body fat constitutes an independent risk factor for complications in bone fracture healing and aseptic loosening of implants. Although mechanical causes have been widely suggested, we hypothesized that the osteogenic mechano-response of human mesenchymal stem cells (hMSCs) may be altered in obese patients.

Methods: We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism.

Results and interpretation: The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity. Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor. Such an upstream imprinting process mediated by factors tightly related to the donor's fat metabolism, which hampers the mechanosensitivity of hMSCs in obese patients, may be of pathogenetic relevance for the complications associated with obesity that are seen in orthopedic surgery.

Show MeSH
Related in: MedlinePlus