Changes in mechanical loading affect arthritis-induced bone loss in mice

Liphardt, Anna‐Maria; Sehic, Edina; Hannemann, Nicole; Gustafsson, Kristian; Bözec, Aline; Schett, Georg; Engdahl, Cecilia

doi:10.1016/j.bone.2019.115149

Cited by 15 publications

(21 citation statements)

References 33 publications

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“…In contrast, arthritic knees injected with mBSA, showed signs of synovitis, bone erosions and cartilage destruction compared to the non‐arthritic control side (Figure 2C‐D). This is in line with previous studies using this model of AIA 7,27,30 . The presence of untreated or de‐IgG complexes together with mBSA did not affect arthritis induction (Figure 2C‐D).…”

Section: Resultssupporting

confidence: 92%

“…A 3‐graded histological scoring system was used where 1 = mild, 2 = moderate, and 3 = severe. Bone erosions were only evaluated on the bone surfaces in the knee joint as described by Liphardt et al 30 For quantification of osteoclast number and osteoclast surface attached to the bone, the sections were stained and counted for TRAP positive osteoclasts using a Leukocyte Acid Phosphatase Kit (Sigma‐Aldrich, 387A‐1KT). Osteoclasts were quantified in the epiphyseal part of tibia, the area above the growth plate near the affected knee joint.…”

Section: Methodsmentioning

confidence: 99%

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Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis‐mediated bone loss

et al. 2020

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Immunoglobulin G (IgG) is important in clearance and recognition of previously presented antigens and after activation, IgGs can interact with the Fc gamma receptors (FcγRs) on haematopoietic cells, including bone‐resorbing osteoclasts. The pathogenicity of IgG, that is the ability to elicit stimulatory effects via FcγRs, can be modulated by attachment of sugar moieties, including sialic acids. Human IgGs and autoantibodies are associated with bone loss in autoimmune disease. However, the impact of polyclonal murine IgG via FcγRs on bone loss is poorly understood. Here, we investigate if heat‐aggregated activated murine polyclonal IgG complexes have any direct effects on murine osteoclasts and if they modulate arthritis‐mediated bone loss. Using cell cultures of murine osteoclasts, we show that IgG complexes without sialic acids (de‐IgG complexes) enhance receptor activator of nuclear factor kappa‐Β ligand (RANKL)‐stimulated osteoclastogenesis, an effect associated with increased FcγRIII expression. Using an in vivo model of arthritis‐mediated bone loss, where IgG complexes were injected into arthritic knees, no effect on the severity of arthritis or the degree of arthritis‐mediated bone loss was detected. Interestingly, injection of de‐IgG complexes into non‐arthritic knees increased osteoclast formation and enhanced bone erosions. Our findings show that activated de‐IgG complexes have no additive effect on arthritis‐mediated bone loss. However, de‐IgG complexes potentiate murine osteoclastogenesis and enhance local bone erosion in non‐arthritic bones, further confirming the link between the adaptive immune system and bone.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis‐mediated bone loss

et al. 2020

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“…It is well known that bone is responsive to its mechanical environment and that a lack of mechanical stimulation promotes bone loss [7,8]. Loading modalities such as axial loading and whole-body vibration can increase bone mass by activating bone-forming osteoblasts [9,10], as well as inhibiting bone-resorbing osteoclasts [6]. Mechanical loading also suppresses tumor-driven osteolysis by restraining bone resorption [11], inhibits the progression of myeloma in the bone [12], and induces apoptosis of breast cancer cells [13].…”

Section: Introductionmentioning

confidence: 99%

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

Yuan

Liu

Zha

et al. 2021

Cancers

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Bone is mechanosensitive and lipoprotein receptor-related protein 5 (Lrp5)-mediated Wnt signaling promotes loading-driven bone formation. While mechanical loading can suppress tumor growth, the question is whether Lrp5 mediates loading-driven tumor suppression. Herein, we examined the effect of Lrp5 using osteocyte-specific Lrp5 conditional knockout mice. All mice presented noticeable loading-driven tumor suppression in the loaded tibia and non-loaded mammary pad. The degree of suppression was more significant in wild-type than knockout mice. In all male and female mice, knee loading reduced cholesterol and elevated dopamine. It reduced tumor-promoting nexin, which was elevated by cholesterol and reduced by dopamine. By contrast, it elevated p53, TNF-related apoptosis-inducing ligand (TRAIL), and chemerin, and they were regulated reversely by dopamine and cholesterol. Notably, Lrp5 overexpression in osteocytes enhanced tumor suppression, and osteoclast development was inhibited by chemerin. Collectively, this study identified Lrp5-dependent and independent mechanisms for tumor suppression. Lrp5 in osteocytes contributed to the loaded bone, while the Lrp5-independent regulation of dopamine- and cholesterol-induced systemic suppression.

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“…e role of mechanical load in subchondral bone remodeling and injury repair has been of gradual concern. Studies have shown that a suitable mechanical load can effectively inhibit KOA-induced subchondral bone osteoporosis and decrease bone mass [32][33][34], thereby retarding KOA procession. Based on evidence showing that mechanical loads were involved in the pathogenesis in bones and regulated bone remodeling [35,36], biomechanical therapy has become an emerging method for KOA treatment by affecting subchondral bone.…”

mentioning

confidence: 99%

“…As reported previously in numerous studies, enhanced bone resorption was the most typical pathological characteristic of KOA subchondral bone [40], which was manifested by a marked decrease in Tb.N and BV/TV and a marked increase in Tb.Sp [34,41]. e studies clarified that ameliorating the subchondral bone structure of KOA by inhibiting the decrease in Tb.N and BV/TV and the increase in Tb.Sp was an effective approach to relieve KOA cartilage degeneration [42,43].…”

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confidence: 99%

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway

Wang

Guo

Shi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF- κ B receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

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Changes in mechanical loading affect arthritis-induced bone loss in mice

Cited by 15 publications

References 33 publications

Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis‐mediated bone loss

Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis‐mediated bone loss

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway

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