Dataset Information

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

ABSTRACT:

Background

Subchondral bone sclerosis is a major feature of osteoarthritis (OA), and bone marrow mesenchymal stem cells (BMSCs) are presumed to play an important role in subchondral bone sclerosis. Accumulating evidence has shown that stromal cell-derived factor-1α (SDF-1α) plays a key role in bone metabolism-related diseases, but its role in OA pathogenesis remains largely unknown. The purpose of this study was to explore the role of SDF-1α expressed on BMSCs in subchondral bone sclerosis in an OA model.

Methods

In the present study, C57BL/6J mice were divided into the following three groups: the sham control, destabilization of the medial meniscus (DMM), and AMD3100-treated DMM (DMM + AMD3100) groups. The mice were sacrificed after 2 or 8 weeks, and samples were collected for histological and immunohistochemical analyses. OA severity was assessed by performing hematoxylin and eosin (HE) and safranin O-fast green staining. SDF-1α expression in the OA model was measured using an enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (q-PCR), and immunohistochemistry. Micro-CT was used to observe changes in subchondral bone in the OA model. CD44, CD90, RUNX2, and OCN expression in subchondral bone were measured using q-PCR and immunohistochemistry. In vitro, BMSCs were transfected with a recombinant lentivirus expressing SDF-1α, an empty vector (EV), or siRNA-SDF-1α. Western blot analysis, q-PCR, and immunofluorescence staining were used to confirm the successful transfection of BMSCs. The effect of SDF-1α on BMSC proliferation was evaluated by performing a CCK-8 assay and cell cycle analysis. The effect of SDF-1α on the osteogenic differentiation of BMSCs was assessed by performing alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Cyclin D1, RUNX2 and OCN expression were measured using Western blot analysis, q-PCR, and immunofluorescence staining.

Results

SDF-1α expression in the DMM-induced OA model increased. In the DMM + AMD3100 group, subchondral bone sclerosis was alleviated, OA was effectively relieved, and CD44, CD90, RUNX2, and OCN expression in subchondral bone was decreased. In vitro, high levels of SDF-1α promoted BMSC proliferation and increased osteogenic differentiation. Cyclin D1, RUNX2, and OCN expression increased.

Conclusion

The results of this study reveal a new molecular mechanism underlying the pathogenesis of OA. The targeted regulation of SDF-1α may be clinically effective in suppressing OA progression.

SUBMITTER: Meng Z

PROVIDER: S-EPMC10088262 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Meng Zhiqiang Z Xin Lujun L Fan Bosheng B

BMC musculoskeletal disorders 20230410 1

<h4>Background</h4>Subchondral bone sclerosis is a major feature of osteoarthritis (OA), and bone marrow mesenchymal stem cells (BMSCs) are presumed to play an important role in subchondral bone sclerosis. Accumulating evidence has shown that stromal cell-derived factor-1α (SDF-1α) plays a key role in bone metabolism-related diseases, but its role in OA pathogenesis remains largely unknown. The purpose of this study was to explore the role of SDF-1α expressed on BMSCs in subchondral bone scleros ...[more]

PMID: 37038152

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Project description:IntroductionBone marrow lesions (BMLs) are frequently identified by MRI in the subchondral bone in knee osteoarthritis (KOA). BMLs are known to be closely associated with joint pain, loss of the cartilage and structural changes in the subchondral trabecular bone (SCTB). Despite this, understanding of the nature of BMLs at the trabecular tissue level is incomplete. Thus, we used Raman microspectroscopy to examine the biochemical properties of SCTB from KOA patients with presence or absence of BMLs (OA-BML, OA No-BML; respectively), in comparison with age-matched cadaveric non-symptomatic controls (Non-OA CTL).MethodsTibial plateau (TP) specimens were collected from 19 KOA arthroplasty patients (6-Male, 13-Female; aged 56-74 years). BMLs were identified ex-vivo by MRI, using PDFS- and T1-weighted sequences. The KOA specimens were then categorized into an OA-BML group (n = 12; containing a BML within the medial condyle only) and an OA No-BML group (n = 7; with no BMLs identified in the TP). The control (CTL) group consisted of Non-OA cadaveric TP samples with no BMLs and no macroscopic or microscopic evidence of OA-related changes (n = 8; 5-Male, 3-Female; aged 44-80 years). Confocal Raman microspectroscopy, with high spatial resolution, was used to quantify the biochemical properties of SCTB tissue of both the medial and the lateral condyle in each group.ResultsThe ratios of peak intensity and integrated area of bone matrix mineral (Phosphate (v1), Phosphate (v2) and Phosphate (v4)), to surrogates of the organic phase of bone matrix (Amide I, Proline and Amide III), were calculated. Within the medial compartment, the mineral:organic matrix ratios were significantly lower for OA-BML, compared to Non-OA CTL. These ratios were also significantly lower for the OA-BML medial compartment, compared to the OA-BML lateral compartment. There were no group or compartmental differences for Carbonate:Phosphate (v1, v2 and v4), Amide III (α-helix):Amide III (random-coil), Hydroxyproline:Proline, or Crystallinity.ConclusionAs measured by Raman microspectroscopy, SCTB tissue in BML zones in KOA is significantly less mineralized than the corresponding zones in individuals without OA. These data are consistent with those obtained using other methods (e.g. Fourier transform infrared spectroscopy; FTIR) and with the increased rate of bone remodeling observed in BML zones. Reduced mineralization may change the biomechanical properties of the trabecular bone in BMLs and the mechanical interaction between subchondral bone and its overlying cartilage, with potential implications for the development and progression of OA.

Project description:ObjectivesTo determine the association between statin therapy and knee MRI-detected subchondral bone marrow lesion (BML) longitudinal worsening in patients with Heberden's nodes (HNs) as the hallmark of generalized osteoarthritis (OA) phenotype.MethodsAll participants gave informed consent, and IRB approved HIPAA-compliant protocol. We assessed the worsening in BML volume and number of affected subregions in the Osteoarthritis Initiative (OAI) participants with HNs at baseline clinical examination (HN+), using the semi-quantitative MRI Osteoarthritis Knee Scores at baseline and 24 months. Participants were classified according to baseline BML involvement as "no/minimal" (≤ 2/14 knee subregions affected and maximum BML score ≤ 1) or "moderate/severe." Statin users and non-users were selected using 1:1 propensity-score (PS) matching for OA and cardiovascular disease (CVD)-related potential confounding variables. We assessed the association between statin use and increasing BML score and affected subregions using adjusted mixed-effect regression models.ResultsThe PS-matched HN+ participants (63% female, aged 63.5 ± 8.5-year-old) with no/minimal and moderate/severe BML cohorts consisted of 332 (166:166, statin users: non-users) and 380 (190:190) knees, respectively. In the HN+ participants with no/minimal BML, statin use was associated with lower odds of both BML score worsening (odds ratio, 95% confidence interval: 0.62, 0.39-0.98) and increased number of affected subregions (0.54, 0.33-0.88). There was no such association in HN- participants or those HN+ participants with baseline moderate/severe BML.ConclusionIn patients with CVD indications for statin therapy and generalized OA phenotype (HN+), statin use may be protective against the OA-related subchondral bone damage only in the subgroup of participants with no/minimal baseline BML.Key points• Statin use may reduce the risk of subchondral bone damage in specific osteoarthritis patients with a generalized phenotype, minimal subchondral bone damage, and cardiovascular statin indications.

Project description:BackgroundSubchondral bone marrow lesions (BMLs) detected on MRI in knee osteoarthritis (OA) are associated with knee pain. The prevalence and progression of subchondral BMLs are increased by mechanical knee load. However, associations of subchondral BML location with weight-bearing knee pain are currently unknown. In this study, we aim to demonstrate associations of subchondral BML location and size with weight-bearing knee pain in knee OA.MethodsWe analyzed 1412 and 582 varus knees from cross-sectional and longitudinal Osteoarthritis Initiative datasets, respectively. BML scores were semi-quantitatively analyzed with the MRI Osteoarthritis Knee Score for 4 subchondral regions (median and lateral femorotibial, medial and lateral patellofemoral) and subspinous region. Weight-bearing and non-weight-bearing pain scores were derived from WOMAC pain items. Correlation and negative binomial regression models were used for analysis of associations between the BML scores and pain at baseline and changes in the BML scores and changes in pain after 24-month follow-up.ResultsGreater BML scores at medial femorotibial and lateral patellofemoral compartments were associated with greater weight-bearing pain scores, and statistical significance was retained after adjusting for BML scores at the other 4 joint compartments and other OA features, as well as for non-weight-bearing pain, age, sex, and body mass index (BMI) (medial femorotibial; B = 0.08, p = 0.02. patellofemoral; B = 0.13, p = 0.01). Subanalysis revealed that greater medial femorotibial BML scores were associated with greater pain on walking and standing (B = 0.11, p = 0.01, and B = 0.10, p = 0.04, respectively). Lateral patellofemoral BML scores were associated with pain on climbing, respectively (B = 0.14, p = 0.02). Increases or decreases over 24 months in BML score in the medial femorotibial compartment were significantly associated with increases or decreases in weight-bearing pain severity after adjusting for non-weight-bearing pain, age, sex, baseline weight-bearing pain, BMI, and BML at the other 4 joint compartments (B = 0.10, p = 0.01).ConclusionsSubchondral BML size at the medial femorotibial joint compartment was specifically associated with the severity and the change in weight-bearing pain, independent of non-weight-bearing pain, in knee OA. Specific associations of weight-bearing pain with subchondral BMLs in weight-bearing compartments of the knee indicate that BMLs in subchondral bone contribute to biomechanically induced OA pain.

Dataset Information

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Background

Methods

Results

Conclusion

Publications

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Similar Datasets

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