Reduced Proliferation and Osteocalcin Expression in Osteoblasts of Male Idiopathic Osteoporosis

Ruiz-Gaspà, Sílvia; Blanch-Rubiò, Josep; Recasens, M. Ciria; Monfort, Jordi; Tío, Laura; Garcia-Giralt, Natàlia; Nogués, Xavier; Monllau, Joan Carles; Carbonell-Abelló, Jordi; Pérez-Edo, Lluís

doi:10.1007/s00223-010-9336-5

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…Serum turnover markers were within the lower normal male reference range. Our findings of normal to lower bone turnover are in line with several publications on primary male osteoporosis, which support the hypothesis of osteoblast dysfunction as a predominant pathomechanism in men …”

Section: Discussionsupporting

confidence: 92%

Intravenous Treatment With Ibandronate Normalizes Bone Matrix Mineralization and Reduces Cortical Porosity After Two Years in Male Osteoporosis: A Paired Biopsy Study

Misof

Patsch²,

Roschger

et al. 2013

Journal of Bone and Mineral Research

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The spectrum of therapeutic options and the amount of clinical trials for male osteoporosis (mOP) is lower than those for postmenopausal osteoporosis. Therefore, we examined the effects of 24 months of ibandronate (IBN) treatment (3 mg/3 mL intravenously every 3 months) on bone material quality in 19 subjects with mOP within an open-label, single-center, prospective phase III study (Eudract number 2006-006692-20). Patients (median age [25th, 75th percentiles] 53.0 [44.5; 57.0] years) were included if they had low bone mineral density (BMD) and/or at least one low trauma fracture and no secondary cause of osteoporosis. The primary endpoint was to evaluate IBN effects on cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) of paired transiliacal bone biopsies (baseline, 24 months). Secondary endpoints included changes in areal bone mineral density (BMD by dual-energy X-ray absorptiometry [DXA]) and serum markers of bone turnover including type I collagen peptides CrossLaps (CTX), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC). At baseline, cancellous bone matrix mineralization from mOP was lower than published reference data (mean degree of mineralization Cn.CaMean À1.8%, p < 0.01). IBN treatment increased calcium concentrations versus baseline (Cn.CaMean þ2.4%, Ct.CaMean, þ3.0% both p < 0.01), and reduced heterogeneity of mineralization (Cn.CaWidth À14%, p ¼ 0.044; Ct.CaWidth, À16%, p ¼ 0.001), leading to cancellous BMDD within normal range. IBN treatment was associated with a decrease in porosity of mineralized cortical tissue (À25%, p ¼ 0.01); increases in BMD at the lumbar spine, the femoral neck, and the total hip (þ3.3%, þ1.9%, and þ5.6%, respectively, p 0.01); and reductions in CTX (À37.5%), P1NP (À44.4%), and OC (À36.3%, all p < 0.01). Our BMDD findings are in line with the reduction of bone turnover markers and the increase in BMD by IBN in our patients and suggest that the latter mainly reflects the increase in matrix mineralization and the reduction of cortical porosity in this cohort with mOP.

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Section: Discussionsupporting

confidence: 92%

Intravenous Treatment With Ibandronate Normalizes Bone Matrix Mineralization and Reduces Cortical Porosity After Two Years in Male Osteoporosis: A Paired Biopsy Study

Misof

Patsch²,

Roschger

et al. 2013

Journal of Bone and Mineral Research

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“…OP occurs due to an imbalance between osteoclastic bone resorption and osteoblastic bone formation (37). Restoring and maintaining the balance between bone formation and bone resorption is an effective way to treat OP (38,39). Physical exercise is an important stimulus for prevention and treatment of osteoporosis (40,41).…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

et al. 2019

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Osteoporosis (OP) is an age-related bone disease occurring worldwide. Osteoporotic fracture is one of the leading causes of disability and death in elderly patients. MicroRNAs (miRNAs/miRs) are key molecular regulatory factors in bone remodeling processes. The present study investigated the expression and mechanism of miR-135b-5p in patients with osteoporosis. The present results suggested that miR-135b-5p was upregulated in bone tissue fragments of patients with osteoporosis compared with the control patients. MC3T3-E1 cells were used to perform osteogenic differentiation induction. Reverse transcription-quantitative PCR and western blot assay were used to detect the mRNA and protein expression levels of the osteogenic markers osteocalcin (OC), Osterix and alkaline phosphatase (ALP). A specific kit was used for detecting ALP activity. The present results indicated that the mRNA expression levels of OC, Osterix and ALP significantly increased on the 7 and 14th day after osteogenic differentiation induction compared with the control group. Protein expression levels of OC, Osterix and ALP also increased on the 7 and 14th day after induction. ALP assay showed that ALP activity was significantly increased on the 7 and 14th day after induction. In addition, the present study found that miR-135b-5p was downregulated in MC3T3-E1 cells 7 and 14 days after osteogenic differentiation induction. The results of TargetScan analysis and dual luciferase reporter gene assay indicated that runt-related transcription factor 2 (RUNX2) was a direct target gene of miR-135b-5p. RUNX2 was upregulated in MC3T3-E1 cells on the 7 and 14th day after induction. Moreover, the present study found that compared with the osteogenic differentiation induction group, miR-135b-5p mimic significantly decreased OC, Osterix and ALP expression, and reduced ALP activity in MC3T3-E1 cells. However, these reductions were reversed following overexpression of RUNX2. The present results showed that miR-135b-5p mimic significantly reduced cell viability in MC3T3-E1 cells and induced cell apoptosis, and these effects were significantly reversed following RUNX2 overexpression. In summary, the present results suggested that miR-135-5p participated in the occurrence and development of osteoporosis via inhibition of osteogenic differentiation and osteoblast growth by targeting RUNX2. The present study suggested a novel potential target that may faciliate the treatment of osteoporosis, and further study is required to examine this possibility.

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“…Also, as cell apoptosis was not investigated, we cannot exclude that cells from CD36KO mice are more sensitive to apoptosis. Such impaired osteoblastic bone formation caused by decreased number and activity of individual osteoblastic cells was shown to be responsible of reduction of bone mass in male patients with idiopathic osteoporosis [42].…”

Section: Discussionmentioning

confidence: 99%

Low-Bone-Mass Phenotype of Deficient Mice for the Cluster of Differentiation 36 (CD36)

et al. 2013

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Bone tissue is continuously remodeled by bone cells and maintenance of its mass relies on the balance between the processes of resorption and formation. We have reported the expression of numerous scavenger receptors, namely scavenger receptor (SR) class B type I and II (SR-BI and SR-BII), and CD36, in bone-forming osteoblasts but their physiological roles in bone metabolism are still unknown. To unravel the role of CD36 in bone metabolism, we determined the bone phenotype of CD36 knockout (CD36KO) mice and characterized the cell functions of osteoblasts lacking CD36. Weights of CD36KO mice were significantly lower than corresponding wild-type (WT) mice, yet no significant difference was found in femoral nor tibial length between CD36KO and WT mice. Analysis of bone architecture by micro-computed tomography revealed a low bone mass phenotype in CD36KO mice of both genders. Femoral trabecular bone from 1 to 6 month-old CD36KO mice showed lower bone volume, higher trabecular separation and reduced trabeculae number compared to WT mice; similar alterations were noticed for lumbar vertebrae. Plasma levels of osteocalcin (OCN) and N-terminal propeptide of type I procollagen (PINP), two known markers of bone formation, were significantly lower in CD36KO mice than in WT mice, whereas plasma levels of bone resorption markers were similar. Accordingly, histology highlighted lower osteoblast perimeter and reduced bone formation rate. In vitro functional characterization of bone marrow stromal cells and osteoblasts isolated from CD36KO mice showed reduced cell culture expansion and survival, lower gene expression of osteoblastic Runt-related transcription factor 2 (Runx2) and osterix (Osx), as well as bone sialoprotein (BSP) and osteocalcin (OCN). Our results indicate that CD36 is mandatory for adequate bone metabolism, playing a role in osteoblast functions ensuring adequate bone formation.

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Reduced Proliferation and Osteocalcin Expression in Osteoblasts of Male Idiopathic Osteoporosis

Cited by 17 publications

References 39 publications

Intravenous Treatment With Ibandronate Normalizes Bone Matrix Mineralization and Reduces Cortical Porosity After Two Years in Male Osteoporosis: A Paired Biopsy Study

Intravenous Treatment With Ibandronate Normalizes Bone Matrix Mineralization and Reduces Cortical Porosity After Two Years in Male Osteoporosis: A Paired Biopsy Study

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

Low-Bone-Mass Phenotype of Deficient Mice for the Cluster of Differentiation 36 (CD36)

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