The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro

Canalis, Ernesto; Hott, M.; Deloffre, P.; Tsouderos, Y; Marie, Pierre J.

doi:10.1016/8756-3282(96)00080-4

Cited by 452 publications

(282 citation statements)

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“…Previous in vitro studies focused on functional activity of mature osteoblastic cells in response to Sr treatment. 9,10,20 Our recent in vitro study demonstrated that Sr can promote osteogenic differentiation of C3H10T1/2 cells and primary murine BMSCs, suggesting that Sr can also promote the commitment of progenitor cells into osteoblastic lineage. 12 This study prompted us to investigate the in vivo response of BMSCs to Sr treatment.…”

Section: Discussionmentioning

confidence: 99%

“…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 differentiation of BMSCs in vitro, we hypothesized that the anabolic effect of Sr on bone was attributed, at least partially, to the modulation of in vivo differentiation of BMSCs towards osteoblastic lineage.…”

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confidence: 99%

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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%

mentioning

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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“…Strontium ranelate also reduces bone resorption and enhances bone mass and strength in mice, rats and monkeys [135][136][137]. In in vitro studies, strontium ranelate also directly reduced osteoclast differentiation and resorption, whereas it increased pre-osteoblast replication and differentiation [138][139][140][141][142]. Preclinical studies in normal and osteopenic animals provided evidence that the dissociation of bone formation and resorption induced by strontium ranelate have beneficial effects on bone mass and bone quality (i.e., microarchitecture, geometry and intrinsic properties), resulting in a positive bone balance.…”

Section: Drugs/agents That Target Bone Remodellingmentioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

149

112

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Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

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“…Strontium induces preosteobast proliferation and enhances osteoblast activity, as demonstrated by the increase in the expression of several early and late osteoblastic markers, such as type I collagen, alkaline phosphatase, bone sialoprotein, osteocalcin and, ultimately, bone matrix mineralization and nodule formation in bone marrow stromal cell cultures and immature osteoblasts [Canalis et al 1996;Barbara et al 2004;Choudhary et al 2007;Caversazio, 2008, Brennan et al 2009. Moreover, strontium inhibits osteoblast apoptosis and induces terminal differentiation of osteoblasts into osteocytes, as demonstrated by the increase in sclerostin expression [Atkins et al 2009].…”

Section: Determinants At the Cellular And Molecular Level: In Vitro Ementioning

confidence: 99%

A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis

Cianferotti

D’Asta

Brandi

2013

Therapeutic Advances in Musculoskeletal

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Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS ® ) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis.

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The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro

Cited by 452 publications

References 20 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

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis

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