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Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs., IntroductionGuided by genetic and molecular mediators, as well as the local microenvironment, bone marrow mesenchymal stem cells (BMSCs) differentiate into various mature cell types, including adipocytes and osteoblasts (1-3). Age-related [...]

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in [osterix.sup.+] osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss., Introduction Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into various cell types, including adipocytes, chondrocytes, and osteoblasts (1, 2). Age-related osteoporosis is characterized by reduced bone [...]

MicroRNAs (miRNAs) interfere with translation of specific target mRNAs and are thought to thereby regulate many cellular processes. Recent studies have suggested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify a new miRNA (miR-2861) in primary mouse osteoblasts that promotes osteoblast differentiation by repressing histone deacetylase 5 (HDAC5) expression at the posttranscriptional level. miR-2861 was found to be transcribed in ST2 stromal cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-2861 enhanced BMP2-induced osteoblastogenesis, whereas inhibition of miR-2861 expression attenuated it. HDAC5, an enhancer of runtrelated transcription factor 2 (Runx2) degradation, was confirmed to be a target of miR-2861. In vivo silencing of miR-2861 in mice reduced Runx2 protein expression, inhibited bone formation, and decreased bone mass. Importantly, miR-2861 was found to be conserved in humans, and a homozygous mutation in pre-miR-2861 that blocked expression of miR-2861 was shown to cause primary osteoporosis in 2 related adolescents. Consistent with the mouse data, HDAC5 levels were increased and Runx2 levels decreased in bone samples from the 2 affected individuals. Thus, our studies show that miR-2861 plays an important physiological role in osteoblast differentiation and contributes to osteoporosis via its effect on osteoblasts., Introduction MicroRNAs (miRNAs) are a growing class of small (~22 nucleotides), single-stranded noncoding RNAs found in diverse organisms (1). They negatively regulate translation of specific mRNAs by base pairing with [...]

Objectives: CD31hiEMCNhi vessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for CD31 and endomucin, couple angiogenesis and osteogenesis. However, the role of CD31hiEMCNhi vessels in bone regeneration remains unknown. In the present study, we investigated the role of CD31hiEMCNhi vessels in the process of bone regeneration. Materials and Methods: We used endothelial‐specific Krüppel like factor 3 (Klf3) knockout mice and ophiopogonin D treatment to interfere with CD31hiEMCNhi vessel formation. We constructed a bone regeneration model by surgical ablation of the trabecular bone. Immunofluorescence and micro‐computed tomography (CT) were used to detect CD31hiEMCNhi vessels and bone formation. Results: CD31hiEMCNhi vessels participate in the process of bone regeneration, such that endothelial‐specific Klf3 knockout mice showed increased CD31hiEMCNhi vessels and osteoprogenitors in the bone regeneration area, and further accelerated bone formation. We also demonstrated that the natural compound, ophiopogonin D, acts as a KLF3 inhibitor to promote vessels formation both in vitro and in vivo. Administration of ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and accelerated bone healing. Conclusions: Our findings confirmed the important role of CD31hiEmcnhi vessels in bone regeneration and provided a new target to treat bone fracture or promote bone regeneration. [ABSTRACT FROM AUTHOR]

ABSTRACT MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14+ peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14+ PBMCs inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14+ PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

With the increasing aging population, aging‐associated diseases are becoming epidemic worldwide, including aging‐associated metabolic dysfunction. However, the underlying mechanisms are poorly understood. In the present study, we aimed to investigate the role of microRNA miR‐188 in the aging‐associated metabolic phenotype. The results showed that the expression of miR‐188 increased gradually in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) of mice during aging. MiR‐188 knockout mice were resistant to the aging‐associated metabolic phenotype and had higher energy expenditure. Meanwhile, adipose tissue‐specific miR‐188 transgenic mice displayed the opposite phenotype. Mechanistically, we identified the thermogenic‐related gene Prdm16 (encoding PR domain containing 16) as the direct target of miR‐188. Notably, inhibition of miR‐188 expression in BAT and iWAT of aged mice by tail vein injection of antagomiR‐188 ameliorated aging‐associated metabolic dysfunction significantly. Taken together, our findings suggested that miR‐188 plays an important role in the regulation of the aging‐associated metabolic phenotype, and targeting miR‐188 could be an effective strategy to prevent aging‐associated metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs. [ABSTRACT FROM AUTHOR]

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1 ) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin ( Ctsk )-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk + PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk + PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To explore the relationship between the changes of estrogen, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and bone mineral density (BMD) decreasing rate (BDR) at different skeletal regions and examine the effects of hormones levels on BDR., Methods: An age cross-sectional study was conducted in 694 healthy adult women excluded from diseases and drugs affecting bone metabolism. Their age range was 20-80 years. The serum concentrations of FSH, LH and estradiol (E2) were measured with radioimmunoassay. And BDR was measured with a DXA fan-beam bone densitometer at various skeletal regions including lumbar spine, left hip and left forearm., Results: The serum levels of FSH (r = -0.597 to -0.479, all P < 0.01) and LH r = -0.452 to -0.283, all P < 0.01) were significantly negatively correlated with BDR at various skeletal regions. Meanwhile, the serum level of E2 only had slightly positive correlation with hip and distal forearm (r = 0.077 to 0.122, all P < 0.05). After adjusting age and body mass index (BMI), serum FSH still had markedly negative correlation with BDR at various skeletal regions. However, the correlation coefficients became weak. Multiple line regression stepwise analysis revealed that serum FSH was a negative determinant factor of BDR at various skeletal regions: 20%-32% changes in BDR of various skeletal regions were determined by FSH, while LH only produced very small negative effects (0.6%-0.8%) on BDR of lumbar spine. Serum E2 seemed to be a positive determinant factor of skeletal regions and 2.5%-5.4% changes in BDR were determined by E2. The effects of serum FSH on BDR were approximately 3.8-12.8 folds than those of serum E2., Conclusions: BDR is correlated with increased FSH in women. The most critical factor for aging-related BDR is FSH in women while a decreased level of estrogen may be secondary.

The objective of this study was to investigate the relationship between serum levels of OPG, TGF- β 1, and TGF- β 2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35-80 years. Serum levels of OPG, TGF- β 1, and TGF- β 2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r = -0.122 to -0.230, all P = 0.007-0.000) and TGF- β 2 (r = -0.100 to -0.173, all P = 0.029-0.000) and a positive correlation between BDR and serum TGF- β 1 (r = 0.245 - 0.365, all P = 0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF- β 2 and BDR. However, statistically significant correlations between serum TGF- β 1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4-3.7% of BDR variation. Serum TGF- β 1 was a positive determinant of BDR and could explain 5.3-13.3% of BDR variation.

Recently, a membrane-based estrogen receptor (ER), ER-α36, was identified and cloned that transduces membrane-initiated estrogen signaling such as activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show that the postmenopausal level of estradiol (E2) induces mitogenic, antiapoptotic, and antiosteogenic effects and proapoptotic effects in postmenopausal osteoblasts and osteoclasts with high levels of ER-α36 expression, respectively. We also found that ER-α36 mediated the effects of postmenopausal-level E(2) on proliferation, apoptosis, and differentiation of osteoblasts through transient activation of the MAPK/ERK pathway, whereas ER-α36-mediated postmenopausal-level E(2) induces apoptosis of osteoclasts through prolonged activation of the MAPK/ERK pathway with the involvement of reactive oxygen species. We also show that the levels of ER-α36 expression in bone are positively associated with bone mineral density but negatively associated with bone biochemical markers in postmenopausal women. Thus the higher levels of ER-α36 expression are required for preserving bone mass in postmenopausal and menopausal women who become osteoporotic if ER-α36-mediated activities are dysregulated., (© 2011 American Society for Bone and Mineral Research.)

Objective: To study bone mass changes and its mechanisms in murine knockout apolipoprotein E (ApoE-/-)., Methods: Both 28-week-old male ApoE-/- mice (n = 6) and wild-type (WT) mice (n = 10) were euthanized. The trabecular and cortical bone microarchitecture were assessed by micro-CT (microCT) in right distal femur. The total body BMD (bone mineral density) of left femur was determined by dual-energy X-ray absorptiometry (DXA). The serum concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) were analyzed using enzyme-linked immunosorbent assay (ELISA). The left tibias were dissected and fixed in 4% paraformaldehyde after decalcified in 0.15M EDTA buffer for 30 days. And the expressions of OPG and RANKL were detected by immunohistochemical staining., Results: Compared with WT mice, the ApoE-/- mice showed an increased volumetric BMD (294 +/- 38) mg/mm(3), tissue BMD (627 +/- 23) mg/mm(3), BMC (bone mineral content) (0.57 +/- 0.08) mg, bone volume fraction (20.38 +/- 4.74)%, trabecular number (6.67 +/- 0.78) mm(-1), trabecular thickness (0.03 +/- 0.01) mm with an decreased bone surface fraction (69 +/- 18) mm(-1), trabecular separation (0.12 +/- 0.01) and structure mode index (1.73 +/- 0.24). The total body BMD was higher in ApoE-/- mice than WT mice [(0.063 +/- 0.004) g/cm(2) vs (0.056 +/- 0.004) g/cm(2)]. The serum level of OPG was significantly higher in ApoE-/- mice than WT mice [(4.98 +/- 0.97) ng/ml vs (3.54 +/- 0.65) ng/ml]. The results of immunohistochemical staining showed that the OPG expression was at a higher level in bone cell of ApoE-/- mice and RANKL showed no obvious change in either sera or bone cells., Conclusion: A decreased bone resorption causes an increased bone mass in ApoE-/- mice and leads to an imbalanced ratio of OPG/ RANKL.

Objective: To investigate the possible mechanism by which adiponectin influences the osteoclastogenesis., Methods: Human osteoblasts were cultured in vitro and adiponectin of the concentrations 0, 3, 10, and 30 microg/ml were added for 48 hours to investigate the dose-dependent effect on the mRNA and protein expression of osteoprotegerin (OPG) in osteoblasts, and adiponectin of the concentrations 0 or 30 microg/ml was added for 0-48 hours to investigate the time-dependent effect. Fluorescent quantitation PCR and ELISA were used to detect the expression of OPG and receptor activator of nuclear factor-kappaB ligand (RANKL). Other human osteoblasts were cultured with CD14 + peripheral blood mononuclear cells (PBMCs), and incubated together with adiponectin of the concentration of 30 microg/ml for 14 days, and then stained by antitartaric acid phosphatase, a marker enzyme of osteoclast., Results: The expression levels of mRNA and protein of OPG in osteoblasts were 100% +/- 9%, 68% +/- 7%, 47% +/- 8%, and 30% +/- 5%, and (9.2 +/- 0.3), (6.6 +/- 0.4), (4.1 +/- 0.4), and (2.6 +/- 0.4) ng/ml respectively after incubation with adiponectin of the concentrations of 0, 3, 10, and 30 microg/ml for 48 hours. The mRNA and protein expression levels of RANKL were 100% +/- 5%, 165% +/- 8%, 213% +/- 6%, and 316% +/- 10%, and (1.3 +/- 0.2), (2.1 +/- 0.1), (2.3 +/- 0.2), and (2.8 +/- 0.1) ng/ml respectively. Adiponectin inhibited the osteoblast OPG expression and promoted the osteoblast RANKL expression dose- and time-dependently (P < 0.05). Adiponectin induced the osteoclast formation in the coculture systems of osteoblast and PBMCs systems., Conclusion: Adiponectin increases osteoclast formation via stimulating RANKL and inhibiting OPG production in the osteoblasts, which may be one of the mechanisms adiponectin influences the osteoclastogenesis thereby.

Objective: To investigate prospectively the annual bone loss rate at spine, proximal femur and distal radius in females and its relationship to relevant factors., Methods: The bone mineral density (BMD) at anteroposterior lumber, proximal femur and distal radius in 220 women of Mawangdui Township, aged 36 - 60, was measured twice, March to April 2000 and March to April 2004, using a Hologic QDR 4500A fan beam X-ray bone densitometer., Results: The annual bone loss rate was the highest during the period of 1 to 5 years since menopause, showing an annual bone loss of 1.70% at the anteroposterior spine, and 2.21%, 1.92%, and 1.56% at the femoral neck, greater trochanter, and distal radius respectively. Even before menopause bone loss was found at the femoral neck and distal radius. BMD loss at the anteroposterior spine and greater trochanter was found in the peri-menopause group. The bone loss rate was the highest in the early menopause group (1.56%/year, P < 0.01), and became lower, however, not significantly in the late menopause group (0.38%/year, P > 0.05). Age was positively correlated with the annual bone loss rates at the anteroposterior spine, greater trochanter, and distal radius (gamma = 0.223 - 0.547, P < 0.05 - 0.01), and the number of year since menopause was also positively correlated with the annual bone loss rate at anteroposterior spine and greater trochanter (gamma = 0.432 - 0.569 P < 0.05 - 0.01). However, body weight and body mass index were negatively correlated with the annual bone loss rates at the anteroposterior spine, femoral neck, and greater trochanter (gamma = 0.239 - 0.466, P < 0.05 - 0.01)., Conclusion: Annual bone loss varies at different skeletal region. Age, years since menopause, and body weight influence the bone loss at different skeletal regions in females.

Objective: To study the age-related changes of bone formation markers, i.e., serum bone alkaline phosphatase (sBAP) and serum osteocalcin (sOC), bone resorption marker, i.e., cross-linked N-telopeptides of type 1 collagen (sNTX), and bone mineral density (BMD) in healthy men., Methods: Serum sBAP, sOC, and sNTX of 389 randomly selected males, aged 20 - 80, all of Han nationality, were measured by using enzyme-linked immunosorbent (ELISA). Dual energy X-ray densitometer was used to measure the BMD of the lumbar vertebrae, left femoral neck, Ward's triangle, and hip. The relationships of these markers to age were analyzed., Results: (1) The sBAP, sOC, and sNTX were negatively correlated with age, the cubic regression model being better with age-related changes of bone biochemical markers as compared with the other regression models (R(2) = 0.013 - 0.029, P < 0.05); (2) When all subjects were stratified by 10-years, the bone biochemical marker values were the highest in the age group 20 - 29, with the sBAP of 30.9 U/L +/- 12.6 U/L, sOC of 12.6 microg/L +/- 6.2 microg/L, and sNTX of 18.2 micromol/L +/- 6.6 micromol/L; then decreased with aging and to a nadir level in the age group 50 - 59, with the sBAP of 26.9 U/L +/- 8.6 U/L, sOC of 9.2 microg/L +/- 5.3 microg/L, and sNTX of 15.6 micromol/L +/- 6.1 micromol/L. After the age of 60, sNTX increased slightly 16.0 micromol/L +/- 6.1 micromol/L, however, BAP and sOC remained stable; (3) After adjustment for age, height, weight, BMI and smoking, serum BAP was negatively correlated with BMD of multiple skeletal sites. sOC was inversely associated with BMD of multiple skeletal sites except lateral spine; and sNTX was negatively correlated with BMD of the lumbar spine and total hip., Conclusion: Negatively correlated with BMD, sBAP, sOC, and sNTX may be sensitive and relatively specific markers to evaluate age-related changes of bone turnover.

Objective: To investigate the distribution of parathyroid hormone (PTH) gene polymorphisms and the relationships of PTH gene polymorphisms with bone mass and serum bone relative biochemical markers., Methods: Blood samples of 314 normal female volunteers, aged 20 - 80, were collected. Serum PTH, bone alkaline phosphatase (sBAP), cross-linked N-telopeptide of collagen type I (sNTX), cross-linked C-telopeptide of collagen type I (sCTX), osteoprotegerin (OPG) and leptin were determined by ELISA. Polymorphisms of PTH gene were detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme BstBI. BMD (QDR4500A) of the anteroposterior spine (AP), supine lateral spine (Lat), and femoral neck (FN) were measured., Results: (1) The genotype frequency of BB, Bb, and bb were 75.8%, 23.3% and 0.9% respectively in normal females volunteers. The frequencies of RFLP alleles B and b were 87.5% and 12.5% respectively. There was no difference in the polymorphism frequency of PTH gene between the post- and pre menopausal women. (2) There were no significant differences in the BMD of the AP, Lat, and FN and the serum biochemical markers between the BB and Bb genotypes. (3) Multiple stepwise regression analysis showed that PTH did not influence the BMD values., Conclusion: PTH gene polymorphism has no relationship with bone mass and serum bone biochemical markers in normal females.

Objective: To study the serum matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels, and the correlations of MMP-1, MMP-2, and TIMP-1 with bone turn-over markers and bone mineral density (BMD) in aged postmenopausal Chinese women., Methods: The serum MMP-1, MMP-2, TIMP-1, serum bone alkaline phosphatase (BAP), serum osteocalcin (OC), serum cross-linked N-telopeptides of type I collagen (NTX) of 297 Chinese female volunteers aged 48 - 89 were measured using ELISA. BMD were measured using dual energy X-ray absorptiometry in aged postmenopausal Chinese women., Results: (1) There were no significant negative relationships between MMP-1, TIMP-1 and BMD and bone biochemical markers. (2) A weak negative relationships were found between MMP-2 and BMD. Adjusted by age and body weight, the correlation of MMP-2 with BMD of neck of femur and hip disappeared. (3) Positive correlations between MMP-2 and BAP, OC, NTX was found (all r = 0.193, 0.231, 0.249, P < 0.01) (4) Serum MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis (1466 microg/L +/- 313 microg/L) than in age-matched normal controls (1222 microg/L +/- 243 microg/L) and osteopenia subjects (1282 microg/L +/- 220 microg/L)., Conclusion: There are significant correlations between serum MMP-2 and bone metabolism, and MMP-2 may increase with increases in bone-turnover. The increases of serum MMP-2 appear possibly as a concomitant event in high bone turnover state, such as postmenopausal osteoporosis.