Epiberberine inhibits bone metastatic breast cancer-induced osteolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.

From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation.

Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.

Predictive Value of Vertebral Bone Destruction Classification Based on Computed Tomography in Diagnosing on Adult Spinal Tuberculosis.

OBJECTIVE: Although magnetic resonance imaging (MRI) is well-established for evaluation of spinal tuberculosis (TB), the importance of computed tomography (CT) should not be overlooked. The purpose of this study was to determine the characteristics of spinal TB and the relationship between spinal TB and the bone lesion pattern seen on three-dimensional CT images. METHODS: One hundred and sixty-one subjects were divided into a TB-positive group and a TB-negative group based on laboratory (X-pert mycobacterium tuberculosis/ rifampin) results and then subdivided further according to whether the bone lesion pattern seen on three-dimensional CT images was fragmentary, osteolytic, sclerotic, or had no evidence of bone destruction. The diagnostic value of the bone lesion pattern was compared between the TB-positive and TB-negative groups. RESULTS: Ninety-nine of the 161 patients were TB-positive and 62 were TB-negative. Fifty-six (34.8%) of the 161 patients had fragmentary/osteolytic lesions, seventy-four (45.9%) had absolute osteolytic lesions, 13 (8.1%) had osteosclerotic lesions, and 18 (11.2%) had no evidence of bone destruction. The fragmentary/osteolytic lesion pattern was strongly predictive of spinal TB (odds ratio 3.33), and when combined with 3 MRI findings (thin abscess wall, more than one half of the vertebral body destroyed, and subligamentous spread) had an even stronger diagnostic value (odds ratio 15.58). CONCLUSIONS: The absolute osteolytic pattern was the most common of the bone lesion patterns. The fragmentary/osteolytic pattern is highly suggestive of spinal TB, especially when combined with MRI findings of a thin abscess wall, destruction of more than one half of the vertebral body, and subligamentous spread.

Massive bone destruction in a human proximal femur from ancient Nubia.

Massive bone destruction in a human right proximal femur is described and differentially discussed in this case study. The individual was an older adult female buried at the ancient Nubian site of Tombos (modern-day Sudan) dating to the early Napatan/Third Intermediate Period (c. 1069-750 BCE). The right femur displayed a pathologic fracture with extensive lytic destruction and resorption of the entire femoral neck, most of the femoral head, and trochanters. Macroscopic and radiographic analyses revealed cortical thinning of the proximal diaphysis with new bone formation enclosing the medullary cavity. The lesion is eccentrically located involving the anterior aspect of the neck. Numerous vascular channels are apparent in the underlying bone. Sclerotic bone marks the limit of the lesion, and osseous lucency is visible in the radiograph. The individual displayed no other lytic lesions; vertebral osteophytic growth, compression fractures, and Schmorl's nodes were observed along with dental disease typical for older individuals. A traumatic etiology is eliminated due to the extensive osteolysis. Vascular, congenital, and developmental conditions are also not consistent with the observed changes. Expansive osteolytic lesions may have been caused by a cyst. Neoplastic tumors resulting in lytic lesions with a high risk of pathologic fracture are also consistent. There have been few reports of such extensive lytic lesions of the proximal femur in the paleopathological and clinical literature; this case adds an example of this underreported condition.

Titanium particles in peri-implantitis: distribution, pathogenesis and prospects.

Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease's prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.

Expression of MMP-14 and its role in bone destruction in middle ear cholesteatoma: A prospective observational study.

Cholesteatoma is a noncancerous cystic lesion caused by an abnormal growth of keratinizing squamous epithelium which is invasive and capable of destroying structures. A prospective study on the expression of membrane type1-matrix metalloproteinases (MMP-14) and its related influencing factors in middle ear cholesteatoma was conducted to fully understand the pathogenesis of cholesteatoma in the molecular level. We examined the expression of MMP-14 by immunohistochemical staining 39 middle ear cholesteatoma specimens and 10 external auditory meatus epithelial cell specimens. The cholesteatoma specimens were divided into 4 groups according to the degree of destruction of the ossicles during surgery. The associated factors affecting MMP-14 expression were analyzed using statistical methods; The positive expression of MMP-14 in the epithelium of the external auditory canal was significantly different between middle ear cholesteatoma and normal patients (P < .05); Gender, age, and the degree of hearing loss had no statistically significant effect on MMP-14 expression (P > .05); The expression of MMP-14 was positively correlated with the severity of bone destruction (R = 0.535, P < .05); MMP-14 plays an important role in the pathological development of the epithelium of cholesteatoma; MMP-14 expression in middle ear cholesteatoma tissue was not strongly correlated with the level of hearing loss, age or gender, but was positively correlated with the degree of middle ear bone destruction.

The checkpoint inhibitor PD-1H/VISTA controls osteoclast-mediated multiple myeloma bone disease.

Multiple myeloma bone disease is characterized by the development of osteolytic bone lesions. Recent work identified matrix metalloproteinase 13 as a myeloma-derived fusogen that induces osteoclast activation independent of its proteolytic activity. We now identify programmed death-1 homolog, PD-1H, as the bona fide MMP-13 receptor on osteoclasts. Silencing PD-1H or using Pd-1h-/- bone marrow cells abrogates the MMP-13-enhanced osteoclast fusion and bone-resorptive activity. Further, PD-1H interacts with the actin cytoskeleton and plays a necessary role in supporting c-Src activation and sealing zone formation. The critical role of PD-1H in myeloma lytic bone lesions was confirmed using a Pd-1h-/- myeloma bone disease mouse model wherein myeloma cells injected into Pd-1h-/-Rag2-/- results in attenuated bone destruction. Our findings identify a role of PD-1H in bone biology independent of its known immunoregulatory functions and suggest that targeting the MMP-13/PD-1H axis may represent a potential approach for the treatment of myeloma associated osteolysis.

Prominent osteolysis in the maxilla: case report of an odontogenic fibroma mimicking a cyst.

BACKGROUND: Odontogenic fibroma (OF) is a rare benign odontogenic tumor of ectomesenchymal origin, mostly affecting the tooth-bearing portions of the jaws in middle-aged patients. Whilst small lesions tend to be clinically asymptomatic, varying unspecific clinical symptoms occur with an increase in size and may mimic odontogenic or other maxillofacial bone tumors, cysts, or fibro-osseous lesions of the jaws. CASE PRESENTATION: A 31-year-old female patient presented with a hard, non-fluctuating protrusion in the vestibule of the upper right maxilla. It was visualized on cone beam computed tomography (CBCT) as space-occupying osteolysis with the displacement of the floor and facial wall of the maxillary sinus, mimicking a cyst-like lesion. The tissue was surgically removed and identified as an OF in the histopathological examination. One year after the surgery, restitution of regular sinus anatomy and physiological intraoral findings were observed. CONCLUSIONS: This case report emphasizes that rare entities, like the maxillary OF presented, often demonstrate nonspecific clinical and radiological findings. Nevertheless, clinicians need to consider rare entities as possible differential diagnoses and plan the treatment accordingly. Histopathological examination is essential to conclude the diagnosis. OF rarely recur after proper enucleation.

Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone-Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR-II Photothermal Therapy.

Bone is one of the prone metastatic sites of patients with advanced breast cancer. The "vicious cycle" between osteoclasts and breast cancer cells plays an essential role in osteolytic bone metastasis from breast cancer. In order to inhibit bone metastasis from breast cancer, NIR-II photoresponsive bone-targeting nanosystems (CuP@PPy-ZOL NPs) are designed and synthesized. CuP@PPy-ZOL NPs can trigger the photothermal-enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti-tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy-ZOL NPs effectively inhibited the proliferation of tumor cells and bone resorption in the in vitro 3D bone metastases model of breast cancer. In a mouse model of breast cancer bone metastasis, CuP@PPy-ZOL NPs combined with PTT with NIR-II significantly inhibited the tumor growth of breast cancer bone metastases and osteolysis while promoting bone repair to achieve the reversal of osteolytic breast cancer bone metastases. Furthermore, the potential biological mechanisms of synergistic treatment are identified by conditioned culture experiments and mRNA transcriptome analysis. The design of this nanosystem provides a promising strategy for treating osteolytic bone metastases.

Secreted microRNAs in bone metastasis.

Bone metastasis is a common complication in several solid cancers, including breast, prostate, and lung. In the bone microenvironment, metastatic cancer cells disturb bone homeostasis leading to osteolytic or osteosclerotic lesions. Osteolytic lesions are characterized by an increased osteoclast-mediated bone resorption while osteosclerotic lesions are caused by enhanced activity of osteoblasts and formation of poor-quality bone. A common feature in bone metastasis is the complex interplay between the cancer cells and the cells of the bone microenvironment, which can occur already before the cancer cells enter the distant site. Cancer cells at the primary site can secrete soluble factors and extracellular vesicles to bone to create a "pre-metastatic niche" i.e., prime the microenvironment permissive for cancer cell homing, survival, and growth. Once in the bone, cancer cells secrete factors to activate the osteoclasts or osteoblasts and the so called "vicious cycle of bone metastases". These pathological cell-cell interactions are largely dependent on secreted proteins. However, increasing evidence demonstrates that secreted RNA molecules, in particular small non-coding microRNAs are critical mediators of the crosstalk between bone and cancer cells. This review article discusses the role of secreted miRNAs in bone metastasis development and progression, and their potential as non-invasive biomarkers.

Pogostone attenuates osteolysis in breast cancer by inhibiting the NF-kB and JNK signaling pathways of osteoclast.

AIMS: Breast cancer is the most prevalent cancer in females, and approximately 70 % of all patients have evidence of metastatic bone disease, which substantially affects the quality of life and survival rate of breast cancer patients. Osteoporosis has become a global public health problem, and the abnormal activation of osteoclasts is the key to the progression of osteoporosis and the key to both diseases lies in the osteoclasts. Effective drug treatments are lacking and there is an urgent need to explore new drugs. MATERIALS AND METHODS: We observed the effects of pogostone (PO) on osteoclast differentiation, bone resorption function and other indicators, and F-actin ring formation by using Trap staining, SEM and immunofluorescence, and further explored the targets of pogostone in regulating osteoclast differentiation and function using qPCR and Western Blot. In addition, we used CCK 8, Transwell, and flow cytometry to study the effects of pogostone on proliferation, invasion, migration, and apoptosis of MDA-MB-231 cells. Animal models were also constructed for in vivo validation. KEY FINDINGS: Pogostone inhibits osteoclast differentiation, bone resorption, formation of F-actin ring, and the expression of specific genes by attenuated NF-kB degradation and phosphorylation of JNK. In vitro, pogostone suppresses invasion of breast cancer cells, migration, and promotes their apoptosis. In mouse models, pogostone attenuated osteoclast formation and bone resorption, blocked breast cancer cells migration, and supprsed breast cancer-induced osteolysis and ovariectomized (OVX)-mediated osteoporosis. SIGNIFICANCE: These biological functions of pogostone make it a potential drug for treatment of breast cancer-associated bone metastasis in the future.

Mechanoregulation may drive osteolysis during bone metastasis: A finite element analysis of the mechanical environment within bone tissue during bone metastasis and osteolytic resorption.

Metastatic bone disease occurs in 70-80% of advanced breast cancer patients and bone tissue is accepted to have attractive physical properties that facilitate cancer cell attraction, adhesion, and invasion. Bone cells also facilitate tumour invasion by biochemical signalling and through resorption of the bone matrix (osteolysis), which releases factors that further stimulate tumour cell activity. The evolving mechanical environment during tumour invasion might play an important role in these processes, as the activity of both bone and cancer cells is regulated by mechanical cues. In particular bone loss and altered mineralisation have been reported, yet how these alter the mechanical environment local to bone and tumour cells is unknown. The objective of this study is to quantify changes in the mechanical environment within bone tissue, during bone metastasis and osteolytic resorption, using finite element analysis (FEA) models reconstructed from high-resolution µCT images of metastatic mouse bone. In particular, we quantify time-dependent changes in mechanical stimuli, local to and distant from an invading tumour mass, to investigate putative mechanobiological cues for osteolysis during bone metastasis. We report here that in early metastasis (3 weeks after tumour inoculation), there was a decrease in strain distribution within the proximal femur trabecular and distal cortical bone tissue. These changes in the mechanical environment preceded extensive osteolytic destruction, but coincided with the onset of early osteolysis, cortical thickening and mineralisation of proximal and distal femur bone. We propose that early changes in the mechanical environment within bone tissue may activate resorption by osteoclast cells and thereby contribute to the extensive osteolytic bone loss at later stage (6 weeks) bone metastasis.

[Icariin inhibits thioacetamide-induced osteoclast differentiation through RANKL-p38/ERK-NFAT pathway].

This study aims to investigate the therapeutic effect of icariin(ICA) on thioacetamide(TAA)-induced femoral osteolysis in rats. RAW264.7 cells were treated with TAA and ICA. Cell counting kit-8(CCK-8) assay was used to detect cell proliferation, and tartrate-resistant acid phosphatase(TRAP) staining to examine the formation of osteoclasts. The expression of TRAP, cathepsin K, c-FOS, and NFATc1 in RAW264.7 cells was determined by Western blot and immunofluorescence method. Thirty-two SD rats were randomized into the control group, TAA group(intraperitoneal injection of TAA at 300 mg·kg~(-1)), ICA group(gavage of ICA at 600 mg·kg~(-1)) and TAA + ICA group(intraperitoneal injection of TAA at 300 mg·kg~(-1) and gavage of ICA at 600 mg·kg~(-1)). Administration was performed every other day for 6 weeks. Body weight and length of femur were recorded at execution. Pathological injury and osteoclast differentiation of femur were observed based on hematoxylin-eosin(HE) staining and TRAP staining, and the changes of bone metabolism-related indexes alkaline phosphatase(ALP), calcium(Ca), phosphorus(P), magnesium(Mg), and cross-linked N-telopeptide of type Ⅰ collagen(NTX-Ⅰ) in serum were detected. Three-point bending test and micro-CT were applied to evaluate the quality of femur, and Western blot to detect the levels of osteoclast-related proteins TRAP, cathepsin K, RANK, RANKL, p38, p-p38, ERK, p-ERK, JNK, p-JNK, c-Fos, and NFATc1. The results showed ICA could inhibit TAA-induced production of TRAP-positive cells, the expression of osteoclast-related proteins, and nuclear translocation of NFATc1. ICA alleviated the weight loss, reduction of femur length, and growth inhibition induced by TAA in SD rats. ICA ameliorated the decline of femur elastic modulus caused by TAA and significantly restored trabecular bone mineral density(BMD), trabecular pattern factor(Tb.Pf), trabecular number(Tb.N), trabecular thickness(Tb.Th), and structure model index(SMI), thus improving bone structure. Western blot results showed ICA suppressed femoral osteoclast differentiation induced by TAA through RANKL-p38/ERK-NFATc1 signaling pathway. ICA inhibits osteoclast differentiation and prevents TAA-induced osteolysis by down-regulating RANKL-p38/ERK-NFAT signaling pathway.

Novel alendronate-CGS21680 conjugate reduces bone resorption and induces new bone formation in post-menopausal osteoporosis and inflammatory osteolysis mouse models.

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and µCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.

MicroRNA-506 ameliorates breast cancer-induced osteolytic bone metastasis via the NFATc-1 signaling pathway.

Breast cancer is becoming a common life-threatening disease, especially in women, along with higher incidence and mortality. MicroRNA (miR)-506 was reported to participate in breast cancer progression, while the role of miR-506 in breast cancer-induced osteolytic bone metastasis is unclear. In the present study, we found significant downregulation of miR-506 in breast cancer tissues and cell lines. Overexpression of miR-506 notably reduced the proliferative, migratory and invasive rates of MCF7 and MDA-MB-231 cells, and reduced the production of inflammatory factors IL-6 and TNF-α in MCF7 cells. Moreover, overexpression of miR-506 obviously inhibited tumor growth in an in vivo animal model. In addition, overexpression of miR-560 efficiently attenuated breast cancer-induced osteolysis in vivo, which was characterized by increased bone volume/total volume (BT/TV), trabecular number (Tb. N), and trabecular thickness (Tb. Th), as well as the reduced trabecular separation (Tb. Sp). The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) was identified as a downstream target of miR-506, and overexpression of miR-506 could inhibit breast cancer progression by targeting NFATc1. Furthermore, our results showed that NFATc-1 might participate in the inhibition of miR-506 on breast cancer-induced osteolysis. In conclusion, our findings provide insights into understanding the pathogenesis of breast cancer and breast cancer-induced osteolytic bone metastasis, and miR-506 might serve as a novel biomarker for this disease.

Postoperative assessment and management of metallosis and periprosthetic osteolysis in patients treated with metal-on-polyethylene total wrist prostheses.

We analysed the relationship between serum metal ions, radiological periprosthetic osteolysis and the clinical features in a series of 25 patients treated with fourth-generation metal-on-polyethylene total wrist prostheses. The mean implant follow-up was 7 years. Our results show that titanium was the main elevated serum metal ion in patients with the prostheses that we used; elevated serum cobalt or chromium values were infrequent. The risk of loosening was higher in an implant older than 6 years, with more than five periprosthetic osteolysis points according to our radiograph zone system, and serum titanium values between 26 to 31 µg/L. The presence of metallosis pseudotumours does not guarantee but increases the risk of implant failure, which may be asymptomatic or associated with little pain.Level of evidence: IV.

Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis.

There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.

Osteocyte CIITA aggravates osteolytic bone lesions in myeloma.

Osteolytic destruction is a hallmark of multiple myeloma, resulting from activation of osteoclast-mediated bone resorption and reduction of osteoblast-mediated bone formation. However, the molecular mechanisms underlying the differentiation and activity of osteoclasts and osteoblasts within a myelomatous microenvironment remain unclear. Here, we demonstrate that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions. CIITA upregulates the secretion of osteolytic cytokines from osteocytes through acetylation at histone 3 lysine 14 in the promoter of TNFSF11 (encoding RANKL) and SOST (encoding sclerostin), leading to enhanced osteoclastogenesis and decreased osteoblastogenesis. In turn, myeloma cell-secreted 2-deoxy-D-ribose, the product of thymidine catalyzed by the function of thymidine phosphorylase, upregulates CIITA expression in osteocytes through the STAT1/IRF1 signaling pathway. Our work thus broadens the understanding of myeloma-induced osteolysis and indicates a potential strategy for disrupting tumor-osteocyte interaction to prevent or treat patients with myeloma bone disease.