Endogenous n-3 polyunsaturated fatty acids (PUFAs) mitigate ovariectomy-induced bone loss by attenuating bone marrow adipogenesis in FAT1 transgenic mice.

AIM: To investigate the effect of endogenous n-3 polyunsaturated fatty acids (PUFAs) on bone marrow adipogenesis under osteoporosis conditions. METHODS: A mouse osteoporosis model overexpressing the FAT1 gene from Caenorhabditis elegans and converting n-6 PUFAs to n-3 PUFAs endogenously was used. RESULTS: The mice presented significantly lower bone marrow adiposity (adipocyte volume/tissue volume, mean adipocyte number) but increased the bone parameters (bone mineral density, bone mineral content, bone volume/total volume) in the distal femoral metaphysis. CONCLUSION: Endogenous n-3 PUFAs protect bone marrow adipogenesis, which provides a novel drug target.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

Could heterotopic ossification be prevented by varying dietary n-3/n-6 polyunsaturated fatty acid ratio: a novel perspective to its treatment?

Heterotopic ossification (HO) is a common complication following with musculoskeletal trauma and surgical procedures. It usually decreases joint mobility and eventually causes loss of joint function. Despite nonsteroidal anti-inflammatory drugs (NSAIDs), the inhibitor of cyclooxygenase(COX), have been proven to prevent HO effectively via prostaglandin E2 synthesis regulation and modulation of tissue responsiveness to pro-inflammatory signaling, HO prevention is still a matter of debate for clinicians to avoid the side effect of NSAIDs. Interestingly, it is suggested that PGE2 production and pro-inflammatory microenvironment in body could be modified by varying the ratio of the precursor fatty acids in the diet. On account of the effect of dietary (n-6)/(n-3) PUFAs ratio on both COX metabolism and pro-inflammatory cytokines mediated biological responsiveness, we hypothesized lowering dietary (n-6)/(n-3) PUFAs ratio may not only directly reduce the substrate of COX-2 and COX-2 activity, but also partially ameliorate tissue inflammatory responsiveness to cytokines correlated with HO development,exerting an inhibitory effect on PGE2 synthesis to prevent HO formation. The negative role of lowering dietary (n-6)/(n-3) PUFAs ratio on angiogenesis, cytokines-induced apoptosis, inflammatory responsiveness and osteogenesis could also contribute to its action on HO development. If our hypothesis is proved to be corrected, it could be an innovative method to treat HO.

Intra-articular lentivirus-mediated insertion of the fat-1 gene ameliorates osteoarthritis.

Osteoarthritis (OA) is a gradually progressive degenerative disease characterized by gradual inflammatory loss of articular cartilage caused by increased proteolytic catabolism, mediated by interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), matrix metalloproteinase (MMPs), aggrecanases and other proteinases, and reduced anabolism of cartilage components, contributed by interleukin-4 (IL-4), interleukin-10 (IL-10), insulin-like growth factor 1 (IGF-1), transforming growth factor ß (TGF-ß), and bone morphogenetic proteins (BMPs). Substantial studies showed n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit a powerful anti-inflammatory effects in and ex vivo through reducing the production of IL-1 and TNF-α and increasing the expression of IL-4, IL-10, TGF-ß and IGF-1 in OA. Meanwhile, more convincing results are observed in the fat-1 transgenic mice, which are exogenously inserted in a fat-1 gene from Caenorhabditis elegans, which can endogenously convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. Taken together, it has long been realized that dietary supplementation with fish oils that are plentiful of n-3 PUFAs can bring benefits in the treatment of osteoarthritis. Previously two phase I human studies based on in vitro transfer of the cDNA via lentivirus to arthritic joints have confirmed its feasibility and safety in human subjects. Consequently, we hypothesis that directly infect the chondrocytes and synoviocytes with lentivirus carrying the fat-1 gene could be a well therapeutic strategy for OA in humans.