ArticlePloS one2012
Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Effects of intra-articular clodronate in the treatment of knee osteoarthritis: results of a double-blind, randomized placebo-controlled trial.Rheumatology international · 2015Trial
- Conservative treatments of bone marrow lesions.Journal of experimental orthopaedics · 2025Article
- Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis.Scientific reports · 2023Article
- Enhanced Bone Remodeling After Fracture Priming.Calcified tissue international · 2022Article
- The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date.Drug design, development and therapy · 2021Review
- Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways.Therapeutic advances in musculoskeletal disease · 2021Review
- Emerging pharmaceutical therapies for osteoarthritis.Nature reviews. Rheumatology · 2020Review
- Role of the SDF-1/CXCR4 signaling pathway in cartilage and subchondral bone in temporomandibular joint osteoarthritis induced by overloaded functional orthopedics in rats.Journal of orthopaedic surgery and research · 2020Article
- Galectin 3 Deficiency Alters Chondrocyte Primary Cilium Formation and Exacerbates Cartilage Destruction via Mitochondrial Apoptosis.International journal of molecular sciences · 2020Article
- A study on the mechanism of Wnt inhibitory factor 1 in osteoarthritis.Archives of medical science : AMS · 2020Article
- SOST Deficiency Aggravates Osteoarthritis in Mice by Promoting Sclerosis of Subchondral Bone.BioMed research international · 2019Article
- Article
- 17β-Estradiol on the Expression of G-Protein Coupled Estrogen Receptor (GPER/GPR30) Mitophagy, and the PI3K/Akt Signaling Pathway in ATDC5 Chondrocytes In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Wnt10b and Dkk-1 gene therapy differentially influenced trabecular bone architecture, soft tissue integrity, and osteophytosis in a skeletally mature rat model of osteoarthritis.Connective tissue research · 2017Article
- Are estrogen-related drugs new alternatives for the management of osteoarthritis?Arthritis research & therapy · 2016Review
- Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis.International journal of molecular sciences · 2016Article
- On the predictive utility of animal models of osteoarthritis.Arthritis research & therapy · 2015Review
- Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice.Current rheumatology reports · 2015Review
- Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.Arthritis research & therapy · 2015Article
- Loss of sclerostin promotes osteoarthritis in mice via β-catenin-dependent and -independent Wnt pathways.Arthritis research & therapy · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSubchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.
methodsOA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.
resultsBone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2-3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.
conclusionThe inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA.
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