Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Abstract

In the rat model of rheumatoid arthritis, a marked formation of osteoclasts is found in the distal tibia and the metatarsal bone. It was therefore postulated that osteoclast progenitors would be increased in the bone marrow cavities of rats with adjuvant-induced arthritis (AA rats). Bone marrow cells obtained from tibia of AA rats were cultured to form cells in the osteoclast lineage to access the number of osteoclast progenitors. Unexpectedly, only a suppressed level of osteoclast progenitors was detected in the diaphyseal bone marrow of tibia in AA rats. Distribution of osteoclast progenitors in the bone marrow cavity was examined, and it was shown that osteoclast progenitors accumulated in the distal tibia. Macrophage inflammatory protein (MIP)-1a, an osteoclastogenic CC chemokine, was expressed in ED-1-positive macrophages localizing in the distal tibia with marked bone destruction. Chemotaxis studies showed that MIP-1a expressed significant activity towards bone marrow cells. The suppressed level of osteoclastogenesis in bone marrow cells of AA rats was restored to a normal level by the addition of MIP-1a. It was suggested that MIP-1a is involved in the migration of osteoclast progenitors to the distal tibia as well as in osteoclastogenesis in AA rats. In these rats, in situ hybridization of the distal tibia with a high level of bone destruction showed significant expression of Receptor activator nuclear factor jB ligand (RANKL) messenger RNA in aggregates of multinucleated osteoclast-like cells present in the bone marrow cavity, a unique pathological feature for these rats. Migrated osteoclast progenitors are thought to be efficiently differentiated into osteoclasts in response to RANKL expressed by the aggregates of osteoclastlike cells under the influence of the MIP-1a. Such positive-feedback regulation of osteoclastogenesis could result in the highest recruitment of active osteoclasts in the area of marked bone destruction.

Phosphatidylserine-containing liposomes suppress inflammatory bone loss by ameliorating the cytokine imbalance provoked by infiltrated macrophages

“…The CFAinduced clinical symptoms were similar to those in our previous studies. [27][28][29] To focus on the effects of PSLs on AAinduced inflammatory bone loss, systemic treatment with PSLs was begun 10 days after CFA injection, when the inflammation was established without bone destruction in the ankle joint. Treatment with PSLs for 18 days significantly reduced the paw volume and resulted in a marked increase in the synovial thickness of ankle joints in AA rats during the chronic stage, without any significant effect during the acute stage (Figure 1a-c; horizontal bars).…”

“…22 Among anti-inflammatory mediators, including TGF-b1 and PGE 2 , IL-10 is known as the strongest feedback mediator of inflammatory bone loss. 23,24 The paw volume increase of adjuvant arthritic (AA) rat, an animal model of RA, [25][26][27] occurs in two stages: namely an acute inflammation stage from 10 to 21 days after complete Freund's adjuvant (CFA) injection, and the chronic bone/ joint destruction stage thereafter. Therefore, in our previous study, to examine the direct effect of PSLs on osteoclastogenesis, the treatment of PSLs was started prior to the formation of osteoclasts in AA rats (14 days after CFA injection).…”

Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis

“…26 Five-week-old female Lewis rats were anesthetized with diethyl ether and were intradermally injected at the base of the tail with complete Freund adjuvant (CFA) containing 25 mg/kg heat-killed M. butyricum (Difco Laboratories) suspended in mineral oil. In control experiments, rats were injected with mineral oil alone.…”

“…25 MIP-1a is highly expressed in the areas of severe bone destruction of the distal tibia of AA-rats. 26 MIP-1a is also involved in pathological osteoclastogenesis associated with multiple myeloma. 27,28 Another chemokine, stromal-derived factor 1 a (SDF-1a/CXCL12), a CXC chemokine having potential ability to support hematopoietic stem cells and progenitors, 29 has the ability to promote migration of inflammatory cells in vitro.…”

A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats

“…14,15 We have previously shown lines of evidence suggesting the involvement of the chemokine MIP-1a in the process of bone destruction accompanying adjuvant-induced arthritis (AA) in rats. 16 Recently, it has been reported that anti-inflammatory drugs such as leflunomide, tacrolimus, and cyclosporine A suppress bone destruction through direct inhibition of RANKL-mediated osteclastogenesis. 17,18 These findings are suggesting the availability of anti-inflammatory drugs or cytokines as the suppressor of bone destruction.…”