Osteoporosis and the Replacement of Cell Populations of the Marrow by Adipose Tissue

Meunier, Pierre J.; Aaron, Jean E.; Edouard, C.; Vignon, G

doi:10.1097/00003086-197110000-00021

Cited by 715 publications

(457 citation statements)

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“…1,22 Clinical observations demonstrated that an increase of adipose tissue is accompanied with a decrease in trabecular bone in aging and postmenopausal women. 23,24 In vitro studies have also suggested an inverse relationship between osteogenic and adipogenic differentiation of BMSCs. 25 Therefore, the increased adipocyte numbers may occur at the expense of diminished osteoblast numbers in the context of aging or postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Peng

Liu

Wang

et al. 2010

Journal Orthopaedic Research

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ABSTRACT:In vitro studies have demonstrated that strontium (Sr) could increase osteogenic differentiation of bone marrow stromal cells (BMSCs). We investigated the in vivo effect of Sr on BMSCs. Thirty-six female rats were randomly divided into the following groups: sham operated and treated with either vehicle (Sham þ Veh) or Sr compound (Sham þ Sr) and ovariectomized and treated with either vehicle (OVX þ Veh) or Sr compound (OVX þ Sr). Vehicle and Sr were orally administrated daily starting immediately after the surgery and continuing for 12 weeks. The anabolic effect of Sr on trabecular bone was determined at the structural and tissue level by microCT and histomorphometry, respectively. Colony formation assays demonstrated that BMSCs exhibited higher osteogenic colony but lower adipogenic colony in Sr-treated versus Veh-treated OVX rats. The mRNA level of osteogenic genes was higher, while the mRNA level of adipogenic genes was lower in BMSCs from Sr-treated versus Veh-treated Sham and OVX rats. The effect of Sr on rat BMSCs was reproducible in human BMSCs. Taken together, this study suggests that the anabolic effect of Sr on normal or osteoporotic bones is associated with increased osteoblastic differentiation of BMSCs. Keywords: strontium; osteoblastogenesis; adipogenesis; bone marrow stromal cells; osteoporosis Bone marrow stromal cells (BMSCs) can differentiate into a number of lineages, including osteoblasts, chondroblasts, and adipocytes. 1 This multipotent differentiation potential makes them good candidates to regenerate degenerating tissues and restore their function. Recent studies suggest that low magnitude mechanical signals can increase bone volume and reduce fat tissues in male mice by stimulating BMSCs proliferation and differentiation into an osteoblast lineage. 2 Moreover, Bortezomib (Bzb), a first-in-class proteasome inhibitor used to treat myeloma patients, exerts an anabolic effect on bone by stimulating the differentiation of BMSCs into osteoblasts, thus leading to new bone formation. 3 These studies indicate that modulation of in vivo lineage differentiation of BMSCs is a feasible approach to build bone volume, which may serve as a new strategy to treat postmenopausal osteoporosis.Strontium ranelate (SR), a new anti-osteoporosis agent, can decrease vertebral and nonvertebral fracture risks in postmenopausal women. [4][5][6] Previous studies on postmenopausal women showed that the serum bone formation marker was increased due to SR treatment as compared to placebo controls. 4 In OVX rats, SR treatment prevented bone loss by increasing the bone formation maker and decreasing the bone resorption marker. 7,8 The cellular and molecular mechanism of the anabolic effect of strontium (Sr) on bone remains poorly understood. In vitro studies suggest that Sr can promote osteoblast proliferation and differentiation. 9,10 Recent studies also demonstrated that Sr can increase in vitro osteogenic differentiation of BMSCs. 11,12 Based on the observation that Sr could increase osteoblastic differentiati...

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Section: Discussionmentioning

confidence: 99%

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Peng

Liu

Wang

et al. 2010

Journal Orthopaedic Research

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“…: performed research; L.M., S.G., J.T., A.D., and J.K.: analyzed data; G.K.: wrote paper. switch'') [12], while others show the opposite [13]. Regarding growth rates, a significant decrease in MSCs from older donors was reported [14,15], while another study shows an increase of more than three times in the proliferation rate of MSCs from older animals [16].…”

Section: Introductionmentioning

confidence: 99%

Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton

et al. 2009

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Progenitor cells such as mesenchymal stem cells (MSCs) have elicited great hopes for therapeutic augmentation of physiological regeneration processes, e.g., for bone fracture healing. However, regeneration potential decreases with age, which raises questions about the efficiency of autologous approaches in elderly patients. To elucidate the mechanisms and cellular consequences of aging, the functional and proteomic changes in MSCs derived from young and old Sprague-Dawley rats were studied concurrently. We demonstrate not only that MSC concentration in bone marrow declines with age but also that their function is altered, especially their migratory capacity and susceptibility toward senescence. High-resolution two-dimensional electrophoresis of the MSC proteome, under conditions of in vitro self-renewal as well as osteogenic stimulation, identified several agedependent proteins, including members of the calponin protein family as well as galectin-3. Functional annotation clustering revealed that age-affected molecular functions are associated with cytoskeleton organization and antioxidant defense. These proteome screening results are supported by lower actin turnover and diminished antioxidant power in aged MSCs, respectively. Thus, we postulate two main reasons for the compromised cellular function of aged MSCs: (a) declined responsiveness to biological and mechanical signals due to a less dynamic actin cytoskeleton and (b) increased oxidative stress exposure favoring macromolecular damage and senescence. These results, along with the observed similar differentiation potentials, imply that MSC-based therapeutic approaches for the elderly should focus on attracting the cells to the site of injury and oxidative stress protection, rather than merely stimulating differentiation.

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“…Recent evidence indicates that thermogenic brown fat decreases with age and this change contributes to obesity (Nedergaard et al 2007;Cypess et al 2009;van Marken Lichtenbelt et al 2009;Virtanen et al 2009). Furthermore, biological aging is associated with increased bone marrow adipogenesis, an etiologic factor underlying osteopenia and osteoporosis (Meunier et al 1971;Gimble et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Biological aging alters circadian mechanisms in murine adipose tissue depots

Sutton

Ptitsyn

Floyd

et al. 2012

AGE

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Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy.The current study compared cohorts of younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the AGE (2013) 35:533-547 DOI 10.1007 Electronic supplementary material The online version of this article (doi:10.1007/s11357-012-9389-7) contains supplementary material, which is available to authorized users. brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erbα were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3β, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.

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Osteoporosis and the Replacement of Cell Populations of the Marrow by Adipose Tissue

Cited by 715 publications

References 0 publications

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton

Biological aging alters circadian mechanisms in murine adipose tissue depots

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